CoChat
Sign Up
Cited by 327Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsRNA Interference and Gene Delivery

pH ‐Sensitive stimulus‐responsive nanocarriers for targeted delivery of therapeutic agents

Open access
Karimi, Mahdi, Eslami, Masoud, Sahandi‐Zangabad, Parham, Mirab, Fereshteh, Farajisafiloo, Negar, Shafaei, Zahra, Ghosh, Deepanjan, Bozorgomid, Mahnaz +2 more·2016·WIREs Nanomedicine and Nanobiotechnology
DOI 10.1002/wnan.1389PMC PMC4945487
Open this paper in CoChat — free account

Abstract

In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH ‐sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH ‐sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co‐delivery of cargos, dual pH ‐sensitive nanocarriers, dual/multi stimuli‐responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer's. In order to design an optimized system, it is necessary to understand the various pH ‐responsive micro/nanoparticles and the different mechanisms of pH ‐sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers. WIREs Nanomed Nanobiotechnol 2016, 8:696–716. doi: 10.1002/wnan.1389 This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/wnan.1389

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Anti-inflammatory agents such as dexamethasone are encapsulated within PDA nanocapsules and conjugated through pH-sensitive linkages, including hydrazone bonds.

    “In a representative strategy, anti-inflammatory agents, such as dexamethasone, are encapsulated within PDA nanocapsules and conjugated through pH-sensitive linkages, including hydrazone bonds.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [76]

    In “Polymeric Nanocarriers” (page unavailable), the paper describes drug encapsulation and pH-sensitive polymer–drug conjugation, including an acid-labile hydrazine linkage used with doxorubicin. It does not describe dexamethasone in PDA nanocapsules or establish a hydrazone linkage for that proposed combination. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • PDA-based nanocarriers with pH-responsive drug release behavior have been extensively developed.

    “pH-responsive release: PDA-based nanocarriers with pH-responsive drug release behavior have been extensively developed, as shown in Figure 6.76,77”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [76]

    The Inorganic NPs section (page unavailable) describes a PDA-coated nanocarrier that released doxorubicin in acidic media, supporting the pH-responsive release claim. It gives one PDA-based example, however, and does not establish that PDA-based nanocarriers have been extensively developed. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In vitro antibacterial assays, simplified biofilm models, release studies, and selected animal models show that PDA-based systems can achieve biofilm inhibition, ROS regulation, localized drug release, photothermal/photodynamic antibacterial effects, and inflammation control.

    “In vitro antibacterial assays, simplified biofilm models, release studies, and selected animal models show biofilm inhibition, ROS regulation, localized drug release, photothermal/photodynamic antibacterial effects, and inflammation control.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [76]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 153 · Cited by 327

Research works printed but not linked: 118

  1. [3]Dong K Dong Y You C Xu W Huang X Yan Y Zhang L Wang K Xing J Assessment of the safety, targeting, and distribution characteristics of a novel pH-sensitive hydrogel Colloids Surf B Biointerfaces 2014 123 965 973 25465751
  2. [4]Chiang C-Y Chu C-C Synthesis of photoresponsive hybrid alginate hydrogel with photo-controlled release behavior Carbohydr Polym 2014 119 18 25 25563940
  3. [5]Indermun S Choonara YE Kumar P du Toit LC Modi G Luttge R Pillay V An interfacially plasticized electro-responsive hydrogel for transdermal electro-activated and modulated (TEAM) drug delivery Int J Pharm 2014 462 52 65 24257244
  4. [6]Karthik S Puvvada N Kumar BN Rajput S Pathak A Mandal M Singh ND Photoresponsive coumarin-tethered multifunctional magnetic nanoparticles for release of anticancer drug ACS Appl Mater Interfaces 2013 5 5232 5238 23730930
  5. [7]Cavalieri F Micheli L Kaliappan S Teo BM Zhou M Palleschi G Antimicrobial and biosensing ultrasound responsive lysozyme-shelled microbubbles ACS Appl Mater Interfaces 2013 5 464 471 23265433
  6. [8]Rapoport NY Kennedy AM Shea JE Scaife CL Nam K-H Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles J Control Release 2009 138 268 276 19477208 PMC2746980
  7. [11]Liua J Huanga Y Kumara A Tanc A Jina S Mozhia A Lianga X pH-sensitive nano-systems for drug delivery in cancer therapy Biotechnol Adv 2014 32 693 710 24309541
  8. [13]Kim JH Yoon LS Nam DH Ryu J Ku SH Park CB Biosensors and bioelectronics self-assembled, photoluminescent peptide hydrogel as a versatile platform for enzyme-based optical biosensors Biosens Bioelectron 2011 26 1860 1865 20171868
  9. [15]Engin K Leeper DB Cater JR Thistlethwaite AJ Tupchong L McFarlane JD Extracellular pH distribution in human tumours Int J Hyperthermia 1995 11 211 216 7790735
  10. [16]Iemma F Spizzirri UG Puoci F Muzzalupo R Trombino S Cassano R Leta S Picci N pH-sensitive hydrogels based on bovine serum albumin for oral drug delivery Int J Pharm 2006 312 151 157 16490328
  11. [17]Shaikh RP Pillay V Choonara YE du Toit LC Ndesendo VM Bawa P Cooppan S A review of multi-responsive membranous systems for rate-modulated drug delivery AAPS PharmSciTech 2010 11 441 459 20300895 PMC2850454
  12. [18]Alvarez-Lorenzo C Concheiro A Smart drug delivery systems: from fundamentals to the clinic Chem Commun 2014 50 7743 7765 24805962
  13. [19]Alvarez-Lorenzo C Concheiro A Chapter 1: From drug dosage forms to intelligent drug delivery systems: a change of paradigm Smart Mater Drug Deliv 2013 1 1 10.1039/9781849736800-00001 · DOI
  14. [20]Binauld S Stenzel MH Acid-degradable polymers for drug delivery: a decade of innovation Chem Commun 2013 49 2082 102 23320254
  15. [22]De Las Heras Alarcon C Pennadam S Alexander C Stimuli responsive polymers for biomedical applications Chem Soc Rev 2005 34 276 285 15726163
  16. [23]Schmaljohann D Thermo- and pH-responsive polymers in drug delivery Adv Drug Deliv Rev 2006 58 1655 1670 17125884
  17. [24]d’Angelo I Conte C Miro A Quaglia F Ungaro F Core-shell nanocarriers for cancer therapy. Part I: biologically oriented design rules Expert Opin Drug Deliv 2014 11 283 297 24313282
  18. [25]Nicolas J Mura S Brambilla D Mackiewicz N Couvreur P Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery Chem Soc Rev 2013 42 1147 1235 23238558
  19. [26]Bickerton S Jiwpanich S Thayumanavan S Interconnected roles of scaffold hydrophobicity, drug loading, and encapsulation stability in polymeric nanocarriers Mol Pharm 2012 9 3569 3578 23088589 PMC3593949
  20. [27]Kamaly N Xiao Z Valencia PM Radovic-Moreno AF Farokhzad OC Targeted polymeric therapeutic nanoparticles: design, development and clinical translation Chem Soc Rev 2012 41 2971 3010 22388185 PMC3684255
  21. [28]Mura S Nicolas J Couvreur P Stimuli-responsive nanocarriers for drug delivery Nat Mater 2013 12 991 1003 24150417
  22. [29]Cheng R Meng F Deng C Klok H-A Zhong Z Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery Bio-materials 2013 34 3647 3657 23415642
  23. [30]Reisner E Arion VB Guedes da Silva MF Lichtenecker R Eichinger A Keppler BK Kukushkin VY Pombeiro AJ Tuning of redox potentials for the design of ruthenium anticancer drugs – an electrochemical study of [ trans-RuCl 4 L (DMSO)] - and indazole Inorg Chem 2004 43 7083 7093 15500346
  24. [31]Hu J Zhang G Liu S Enzyme-responsive polymeric assemblies, nanoparticles and hydrogels Chem Soc Rev 2012 41 5933 5949 22695880
  25. [32]Vyas SP Singh A Sihorkar V Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting Crit Rev Ther Drug Carrier Syst 2001 18 1 1 76 11326743
  26. [33]Hayashi K Ono K Suzuki H Sawada M Moriya M Sakamoto W Yogo T High-frequency, magnetic-field-responsive drug release from magnetic nanoparticle/organic hybrid based on hyperthermic effect ACS Appl Mater Interfaces 2010 2 1903 1911 20568697
  27. [34]Prabhakar U Maeda H Jain RK Sevick-Muraca EM Zamboni W Farokhzad OC Barry ST Gabizon A Grodzinski P Blakey DC Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology Cancer Res 2013 73 2412 2417 23423979 PMC3916009
  28. [35]Li Y Wang J Wientjes MG Au JL-S Delivery of nanomedicines to extracellular and intracellular compartments of a solid tumor Adv Drug Deliv Rev 2012 64 29 39 21569804 PMC3378679
  29. [36]Less JR Skalak TC Sevick EM Jain RK Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions 1991 1988088
  30. [38]Jain RK Transport of molecules in the tumor interstitium: a review Cancer Res 1987 500 3039 3052 3555767
  31. [39]Rofstad EK Galappathi K Mathiesen BS Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis Neoplasia 2014 16 586 594 25117980 PMC4198829
  32. [43]Curti BD Urba WJ Alvord WG Janik JE Smith JW 2nd Madara K Longo DL Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: changes during treatment Cancer Res 1993 53 10 2204 2207 8485703
  33. [44]Matsumura Y Maeda H A new concept for macro-molecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs Cancer Res 1986 46 12 part 1 6387 6392 2946403
  34. [45]Maeda H Sawa T Konno T Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS J Control Release 2001 74 47 61 11489482
  35. [46]Roberts WG Palade GE Neovasculature induced by vascular endothelial growth factor is fenestrated Cancer Res 1997 57 765 772 9044858
  36. [47]Ivanovic Z Hypoxia or in situ normoxia: The stem cell paradigm J Cell Physiol 2009 219 271 275 19160417
  37. [50]Mahmoudi M Lynch I Ejtehadi MR Monopoli MP Bombelli FB Laurent S Protein à nanoparticle interactions: opportunities and challenges 2011 111 9 5610 5637 21688848
  38. [51]Monopoli MP Aberg C Salvati A Dawson KA Bio-molecular coronas provide the biological identity of nanosized materials Nat Nanotechnol 2012 7 779 786 23212421
  39. [53]Volk T Jaihdel E Fortmeyer HP Glisenkampl K Rajewskyl MF pH in human tumour xenografts: effect of intravenous administration of glucose Br J Cancer 1993 68 3 492 500 8353039 PMC1968383
  40. [54]Criscione JM Le BL Stern E Brennan M Rahner C Papademetris X Fahmy TM Self-assembly of pH-responsive fluorinated dendrimer-based particulates for drug delivery and noninvasive imaging Biomaterials 2009 30 3946 3955 19443028
  41. [55]Vaupel P The role of hypoxia-induced factors in tumor progression Oncologist 2004 9 10 17 15591418
  42. [56]Naha PC Bhattacharya K Tenuta T Dawson KA Lynch I Gracia A Lyng FM Byrne HJ Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480) Toxicol Lett 2010 198 134 143 20600712
  43. [57]DeBerardinis RJ Lum JJ Hatzivassiliou G Thompson CB The biology of cancer: metabolic reprogramming fuels cell growth and proliferation Cell Metab 2008 7 11 20 18177721
  44. [59]Kim J-W Dang CV Cancer’s molecular sweet tooth and the Warburg effect Cancer Res 2006 66 8927 8930 16982728
  45. [60]Kojima C A collagen-mimic dendrimer capable of controlled release J Am Chem Soc 2009 131 6052 6053 19354246
  46. [61]Giatromanolaki A Koukourakis MI Sivridis E Pastorek J Wykoff CC Gatter KC Harris AL Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer Cancer Res 2001 61 21 7992 7998 11691824
  47. [62]Tian L Bae YH Cancer nanomedicines targeting tumor extracellular pH Colloids Surf B Biointerfaces 2012 99 116 126 22078927 PMC3345308
  48. [63]Gatenby RA Gillies RJ Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004 4 891 899 15516961
  49. [64]Bae Y Nishiyama N Fukushima S Koyama H Yasuhiro M Kataoka K Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy Bio-conjug Chem 2005 16 122 130 15656583
  50. [65]Manchun S Dass CR Sriamornsak P Targeted therapy for cancer using pH-responsive nanocarrier systems Life Sci 2012 90 381 387 22326503
  51. [66]Mellman I Fuchs R Helenius A Acidification of the endocytic and exocytic pathways Annu Rev Biochem 1985 55 663 700 2874766
  52. [67]Cerletti a Drewe J Fricker G Eberle aN Huwyler J Endocytosis and transcytosis of an immunoliposome-based brain drug delivery system J Drug Target 2000 8 435 446 11328669
  53. [68]Bareford LM Swaan PW Endocytic mechanisms for targeted drug delivery Adv Drug Deliv Rev 2007 59 748 758 17659804 PMC2000329
  54. [69]Couvreur P Vauthier C Nanotechnology: intelligent design to treat complex disease Pharm Res 2006 23 1417 1450 16779701
  55. [70]Quader S Cabral H Mochida Y Ishii T Liu X Toh K Kinoh H Miura Y Nishiyama N Kataoka K Selective intracellular delivery of proteasome inhibitors through pH-sensitive polymeric micelles directed to efficient antitumor therapy J Control Release 2014 188 67 77 24892974
  56. [71]Hatakeyama H Murata M Sato Y Takahashi M Minakawa N Matsuda A Harashima H The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice J Control Release 2013 173 43 50 24511611
  57. [72]Madhusudana Rao K Krishna Rao KSV Ramanjaneyulu G Ha C-S Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti cancer drug delivery Int J Pharm 2015 478 788 795 25528297
  58. [73]Zou J Zhang F Zhang S Pollack SF Elsabahy M Fan J Wooley KL Poly(ethylene oxide)-block-poly-phosphoester-graft-paclitaxel conjugates with acid-labile linkages as a pH-sensitive and functional nanoscopic platform for paclitaxel delivery Adv Healthc Mater 2014 3 441 448 23997013 PMC3938983
  59. [74]Mukhopadhyay P Chakraborty S Bhattacharya S Mishra R Kundu PP pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery Int J Biol Macromol 2015 72 640 648 25239194
  60. [76]Chacko RT Ventura J Zhuang JM Thayumanavan S Polymer nanogels: a versatile nanoscopic drug delivery platform Adv Drug Deliv Rev 2012 64 836 851 22342438 PMC3359494
  61. [78]Soni G Yadav KS Nanogels as potential nanomedicine carrier for treatment of cancer: a mini review of the state of the art Saudi Pharm J 2014 In Press PMC4792897 27013905
  62. [79]Yallapu MM Jaggi M Chauhan SC Design and engineering of nanogels for cancer treatment Drug Discov Today 2001 16 457 463 21414419 PMC3095726
  63. [80]Vinogradov SV Colloidal microgels in drug delivery applications Curr Pharm Des 2006 12 4703 4712 17168773 PMC1764637
  64. [83]Lv Y Huang H Yang B Liu H Li Y Wang J A robust pH-sensitive drug carrier: aqueous micelles mineralized by calcium phosphate based on chitosan Carbohydr Polym 2014 111 101 107 25037334
  65. [85]Kataoka K Harada A Nagasaki Y Block copolymer micelles for drug delivery: design, characterization and biological significance Adv Drug Deliv Rev 2001 47 113 131 11251249
  66. [86]Yang YQ Zhao B Li ZD Lin WJ Zhang CY Guo XD Wang JF Zhang LJ pH-sensitive micelles self-assembled from multi-arm star triblock copolymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) for controlled anticancer drug delivery Acta Biomater 2013 9 7679 7690 23669619
  67. [87]Liu GY Li M Zhu CS Jin Q Zhang ZC Ji J Charge-conversional and pH-sensitive PEGylated polymeric micelles as efficient nanocarriers for drug delivery Macromol Biosci 2014 14 1280 1290 24866398
  68. [89]Lv S Tang Z Zhang D Song W Li M Lin J Liu H Chen X Well-defined polymer-drug conjugate engineered with redox and pH-sensitive release mechanism for efficient delivery of paclitaxel J Control Release 2014 194 220 227 25220162
  69. [90]Zou J Jafr G Themistou E Yap Y Wintrob ZA Alexandridis P Ceacareanu AC Cheng C pH-Sensitive brush polymer-drug conjugates by ring-opening metathesis copolymerization Chem Commun (Camb) 2011 47 15 4493 4495 21399797
  70. [91]She W Li N Luo K Guo C Wang G Geng Y Gu Z Dendronized heparin-doxorubicin conjugate based nanoparticle as pH-responsive drug delivery system for cancer therapy Biomaterials 2013 34 2252 2264 23298778
  71. [92]Du C Deng D Shan L Wan S Cao J Tian J Achilefu S Gu Y A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery Biomaterials 2013 34 3087 3097 23374705
  72. [93]Soppimath K Aminabhavi T Kulkarni A Rudzinski W Biodegradable polymeric nanoparticles as drug delivery devices J Control Release 2001 70 1 20 11166403
  73. [94]Liu R Li D He B Xu X Sheng M Lai Y Wang G Gu Z Anti-tumor drug delivery of pH-sensitive poly (ethylene glycol)-poly (L-histidine-)-poly (L-lactide) nanoparticles J Control Release 2011 152 49 56 21397642
  74. [95]Dan X Wu F Chen Y Wei L Yuan W pH-sensitive degradable nanoparticles for highly efficient intracellular delivery of exogenous protein Int J Nanomedicine 2013 8 3405 24039423 PMC3771747
  75. [96]Ramasamy T Haidar ZS Tran TH Choi JY Jeong JH Shin BS Choi HG Yong CS Kim JO Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs Acta Biomater 2014 10 5116 5127 25169256
  76. [97]Blume G Cevc G Liposomes for the sustained drug release in vivo Biochim Biophys Acta Biomembr 1990 1029 91 97 2223816
  77. [100]Sihorkaer V Vyas SP Potential of polysaccharide anchored liposomes in drugs delivery, targeting and immunization J Pharm Pharm Sci 2001 4 138 158 11466172
  78. [101]Yoshizaki Y Yuba E Sakaguchi N Koiwai K Harada A Kono K Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy Biomaterials 2014 35 8186 8196 24969637
  79. [102]Watarai S Iwase T Tajima T Yuba E Kono K Efficiency of pH-sensitive fusogenic polymer-modified liposomes as a vaccine carrier Sci World J 2013 2013 Article ID 903234 7 PMC3575622 23431260
  80. [103]Bersani S Vila-Caballer M Brazzale C Barattin M Salmaso S pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine) decorated liposomes for the delivery of gemcitabine to cancer cells Eur J Pharm Biopharm 2014 88 670 682 25157908
  81. [104]Deng Z Zhen Z Hu X Wu S Xu Z Chu PK Hollow chitosan-silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy Biomaterials 2011 32 4976 4986 21486679
  82. [105]Zheng Q Lin T Wu H Guo L Ye P Hao Y Guo Q Jiang J Fu F Chen G Mussel-inspired polydopamine coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release Int J Pharm 2014 463 22 26 24393764
  83. [107]Tang F Li L Chen D Mesoporous silica nanoparticles: synthesis, biocom-patibility and drug delivery Adv Mater 2012 24 1504 1534 22378538
  84. [108]Kim S Park C Mussel-inspired transformation of CaCO3 to bone minerals Biomaterials 2010 31 6628 6634 20541803
  85. [110]Nowag S Haag R pH-responsive micro- and nanocarrier systems Angew Chem Int Ed 2014 53 49 51 24306995
  86. [112]Shenoy D Little S Langer R Amiji M Poly(ethylene oxide)-modified poly(β-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 2. in vivo distribution and tumor localization studies Pharm Res 2005 22 2107 2114 16254763 PMC1350958
  87. [113]Dan K Pan R Ghosh S Aggregation and pH responsive disassembly of a new acid-labile surfactant synthesized by thiol - acrylate michael addition reaction Langmuir 2011 27 612 617 21158399
  88. [114]Ulbrich K Subr V Polymeric anticancer drugs with pH-controlled activation Adv Drug Deliv Rev 2004 56 1023 1050 15066758
  89. [115]Tomlinson R Heller J Brocchini S Duncan R Polyacetal-doxorubicin conjugates designed for pH-dependent degradation Bioconjug Chem 2003 14 1096 1106 14624622
  90. [116]Torchilin VP Multifunctional nanocarriers Adv Drug Deliv Rev 2012 64 302 315 17092599
  91. [117]Legendre J Szoka FJ Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes Pharm Res 1992 9 1235 1242 1448419
  92. [119]Bae Y Fukushima S Harada A Kataoka K Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change Angew Chem Int Ed Engl 2003 42 4640 4643 14533151
  93. [120]Chen W Meng F Cheng R Zhong Z pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: a comparative study with micelles J Control Release 2010 142 40 46 19804803
  94. [122]Wang X-Q Zhang Q pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs Eur J Pharm Biopharm 2012 82 219 229 22885229
  95. [123]Li MG Lu WL Wang JC Zhang X Zhang H Wang XQ Wu CS Zhang Q Preparation and characterization of insulin nanoparticles employing chitosan and poly(methylmethacrylate/methylmethacrylic acid) copolymer J Nanosci Nanotechnol 2006 6 2874 2886 17048494
  96. [124]Ganta S Devalapally H Shahiwala A Amiji M A review of stimuli-responsive nanocarriers for drug and gene delivery J Control Release 2008 126 187 204 18261822
  97. [125]Zhang S Zhao Y Rapid release of entrapped contents from multi-functionalizable, surface cross-linked micelles upon different stimulation J Am Chem Soc 2010 132 10642 10644 20681683
  98. [126]Qiu Y Park K Environment-sensitive hydrogels for drug delivery Adv Drug Deliv Rev 2001 53 321 339 11744175
  99. [127]Sun X Wang H Jing Z Mohanathas R Hemicellulose-based pH-sensitive and biodegradable hydrogel for controlled drug delivery Carbohydr Polym 2013 92 1357 1366 23399165
  100. [130]Faghihi S Karimi A Jamadi M Imani R Salarian R Graphene oxide/poly(acrylic acid)/gelatin nanocomposite hydrogel: experimental and numerical validation of hyperelastic model Mater Sci Eng C Mater Biol Appl 2014 38 299 305 24656382
  101. [132]Sonaje K Chen YJ Chen HL Wey SP Juang JH Nguyen HN Hsu CW Lin KJ Sung HW Enteric-coated capsules filled with freeze-dried chitosan/poly (γ-glutamic acid) nanoparticles for oral insulin delivery Biomaterials 2010 31 3384 3394 20149435
  102. [133]Carelli V Coltelli S Di Colo G Nannipieri E Serafini MF Silicone microspheres for pH-controlled gastrointestinal drug delivery Int J Pharm 1999 179 73 83 10053204
  103. [134]Ashley CE Carnes EC Phillips GK Padilla D Durfee PN Brown PA Hanna TN Liu J Phillips B Carter MB Carroll NJ Jiang X Dunphy DR Willman CL Petsev DN Evans DG Parikh AN Chackerian B Wharton W Peabody DS Brinker CJ The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers Nat Mater 2011 10 389 397 21499315 PMC3287066
  104. [135]Wu X Wang Z Zhu D Zong S Yang L Zhong Y Cui Y pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles encapsulated in a copolymer-lipid bilayer ACS Appl Mater Interfaces 2013 5 10895 10903 24127854
  105. [136]Torchilin VP Multifunctional, stimuli-sensitive nano-particulate systems for drug delivery Nat Rev Drug Discov 2014 13 813 827 25287120 PMC4489143
  106. [138]Zhou T Zhao X Liu L Liu P Preparation of biodegradable PEGylated pH/reduction dual-stimuli responsive nanohydrogels for controlled release of an anti-cancer drug Nanoscale 2015 7 12051 12060 26118938
  107. [139]Li Z Xu W Wang Y Shah BR Zhang C Chen Y Li Y Li B Quantum dots loaded nanogels for low cytotoxicity, pH-sensitive fluorescence, cell imaging and drug delivery Carbohydr Polym 2015 121 477 485 25659723
  108. [140]Hsieh CJ Chen YC Hsieh PY Liu SR Wu SP Hsieh YZ Hsu HY Graphene oxide based nanocarrier combined with a pH-sensitive tracer: a vehicle for concurrent pH sensing and pH-responsive oligonucleotide delivery ACS Appl Mater Interfaces 2015 7 11467 11475 25945595
  109. [141]Treiber C Quadir MA Voigt P Radowski M Xu S Munter LM Bayer TA Schaefer M Haag R Multhaup G Cellular copper import by nanocarrier systems, intracellular availability, and effects on amyloid β peptide secretion Biochemistry 2009 48 4273 4284 19331399
  110. [142]Tang C Amin D Messersmith PB Anthony JE Prud’homme RK Polymer directed self-assembly of pH-responsive antioxidant nanoparticles Langmuir 2015 31 3612 3620 25760226 PMC4679371
  111. [143]Wang Y Chen L Tan L Zhao Q Luo F Wei Y Qian Z PEG–PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy Biomaterials 2014 35 6972 6985 24836952
  112. [144]Koetting MC Peppas NA pH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) hydrogels with reduced ionic strength loading solutions offer improved oral delivery potential for high isoelectric point-exhibiting therapeutic proteins Int J Pharm 2014 471 83 91 24853463 PMC4096305
  113. [145]Gogoi N Chowdhury D Novel carbon dot coated alginate beads with superior stability, swelling and pH responsive drug delivery J Mater Chem B 2014 2 4089 4099 32261740
  114. [146]Du J-Z Du X-J Mao C-Q Wang J Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery J Am Chem Soc 2011 133 17560 17563 21985458
  115. [147]Yu H Xu Z Chen X Xu L Yin Q Zhang Z Li Y Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes mediating co-delivery of siRNA and paclitaxel Macromol Biosci 2014 14 100 109 23966347
  116. [148]Gui W Wang W Jiao X Chen L Wen Y Zhang X Dual-cargo selectively controlled release based on a pH-responsive mesoporous silica system Chem-PhysChem 2015 16 607 613 25492672
  117. [149]Ju Y Cui J Müllner M Suma T Hu M Caruso F Engineering low-fouling and pH-degradable capsules through the assembly of metal-phenolic networks Biomacromolecules 2015 16 807 814 25654404
  118. [150]Tu F Lee D Shape-changing and amphiphilicity-reversing Janus particles with pH-responsive surfactant properties J Am Chem Soc 2014 136 9999 10006 24791976

Authors
Karimi, M., Eslami, M., Sahandi‐Zangabad, P., Mirab, F., Farajisafiloo, N., Shafaei, Z., Ghosh, D., Bozorgomid, M., Dashkhaneh, F., & Hamblin, M. R.
Affiliations
  • Iran University of Medical Sciences (IR)
  • Sharif University of Technology (IR)
  • Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine Iran University of Medical Sciences Tehran Iran
  • Polymeric Materials Research Group, Department of Materials Science and Engineering Sharif University of Technology Tehran Iran
  • Kharazmi University (IR)
  • University of Tehran (IR)
  • Islamic Azad University Central Tehran Branch (IR)
  • Harvard University (US)
Corresponding author
Hamblin, Michael R.
ORCID
Venue
WIREs Nanomedicine and Nanobiotechnology
Publisher
Wiley
Published
2016-01-14
Volume
8
Issue
5
Pages
696-716
ISSN
  • 1939-0041 (ISSN-L)
  • 1939-5116
DOI
10.1002/wnan.1389
PMC
PMC4945487
OpenAlex
W2237967761
Cited by
327
References
153
Citations by year
2026: 58 · 2025: 68 · 2024: 29 · 2023: 24 · 2022: 20 · 2021: 23 · 2020: 31 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 11
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (R01AI050875)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
pH-sensitive nanocarriers, stimuli-responsive nanocarriers, targeted drug delivery, pH-responsive drug release, anticancer drug delivery, tumor microenvironment, metal ion delivery, protein delivery, insulin delivery, Alzheimer's disease treatment
MeSH terms
Animals, Cell Line, Drug Carriers, Humans, Hydrogen-Ion Concentration, Models, Biological, Mice, Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review