Cited by 1,004Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsDendrimers and Hyperbranched Polymers

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Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review

Kanamala, Manju, Wilson, William R., Yang, Mimi, Palmer, Brian D., Wu, Zimei·2016·Biomaterials

DOI 10.1016/j.biomaterials.2016.01.061

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Abstract

As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy.

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A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.
Matsumura, Y., & Maeda, H. (1986) · PubMed · Cited by 6,781
Long-Circulating and Target-Specific Nanoparticles: Theory to Practice
Moghimi, S. M., Hunter, A. C., & Murray, J. C. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01494-7 · Cited by 3,521
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
Untitled work
(1989) · PubMed · Cited by 3,343
Thermo- and pH-responsive polymers in drug delivery☆
SCHMALJOHANN, D. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.09.020 · Cited by 3,023
To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery
Danhier, F., Féron, O., & Véronique Préat, A. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.08.027 · Cited by 2,891
A review of stimuli-responsive nanocarriers for drug and gene delivery
Ganta, S., Devalapally, H., Shahiwala, A., & Amiji, M. M. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.12.017 · Cited by 2,198
Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications
WICKI, A. N., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.030 · Cited by 1,962
New-Concept Chemotherapy by Nanoparticles of Biodegradable Polymers: Where Are We Now?
Feng, S.-S. (2006) · Nanomedicine · doi:10.2217/17435889.1.3.297 · Cited by 1,951
Lipid polymorphism and the functional roles of lipids in biological membranes
Cullis, P. R., & KRUIJFF, B. D. (1979) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(79)90012-1 · Cited by 1,865

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Show all 213 references

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Research works printed but not linked: 4

Immordino, 2006, Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential, Int. J. Nanomedicine, 1, 297
Liu, 2014, pH-Sensitive nano-systems for drug delivery in cancer therapy, Biotechnol. Adv., 32, 693, 10.1016/j.biotechadv.2013.11.009 · DOI · Paper page
Sun, 2014, Cancer stem cell therapy using doxorubicin conjugated to gold nanoparticles via hydrazone bonds, Biomaterials, 35, 836, 10.1016/j.biomaterials.2013.10.011 · DOI
Carmali, 2014, Chapter 13-polyacetals, 219

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Self-citation
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Background
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Background
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“This enhances electrostatic attraction to the negatively charged tumor cell membranes, facilitating endosomal escape [46,47].”
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“5–7).(60,61) Based on this difference in pH of cancer and healthy tissues, different types of pH-responsive nano-systems are”
Background
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“…significantly more acidic environment (pH 5.7–6.9) due to the presence of lactic acid and perhaps by some end products formed by lung carcinoma cells that is linked to an unusual accelerated metabolism as well as the proliferation in contrast to normal physiological tissues (Kanamala et al. 2016).”
BackgroundInfluential
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“…tissue scaffolds, providing a breakthrough in regenerative medicine and organ transplantation. nanorobotics is emerging as a trans-formative approach, with tiny autonomous robots capable of targeted drug delivery, tissue repair, and the removal of harmful substances at the cellular level [110].”
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“42 In addition, the overexpression of tumor-associated enzymes, such as matrix metalloproteinases, cathepsins, phospholipases, and oxidoreductases, 43 provides another avenue for drug release through enzyme-mediated reactions.”
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Background
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Advanced supramolecular self-assembly for lifecycle-optimized agrochemical delivery
Xiao, Y., Wu, C., Han, M., Chen, P., Zhou, L. Y., & Yin, Q. (2024) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2024.215953 · Cited by 35
Convenient preparation of charge-adaptive chitosan nanomedicines for extended blood circulation and accelerated endosomal escape
Zhang, Y., Li, Y., Ma, J., Wang, X., Yuan, Z., & Wang, W. (2018) · Nano Research · doi:10.1007/s12274-018-2014-z · Cited by 34
“In the search for alternative methods for hydrophilic modifications as mentioned above, surface decoration with anionic polymers, such as poly(acrylic acid) [5], poly(aspartic acid), polysulfonamides, and poly(lactic-co-glycolic acid) [17] have attracted much interest owing to their exceptional resistance against non-…”
Background
Synthesis of strong and highly stretchable, electrically conductive hydrogel with multiple stimuli responsive shape memory behavior
Zhang, X., Cai, J., Liu, W., Liu, W., & Qiu, X. (2019) · Polymer · doi:10.1016/j.polymer.2019.122147 · Cited by 33
Design framework for mechanically tunable soft biomaterial composites enhanced by modified horseshoe lattice structures
Wang, D., Xiong, Y., Zhang, B., Zhang, Y., Rosen, D. W., & Ge, Q. (2020) · Soft Matter · doi:10.1039/c9sm02119a · Cited by 34
Redox-Responsive Coordination Polymers of Dopamine-Modified Hyaluronic Acid with Copper and 6-Mercaptopurine for Targeted Drug Delivery and Improvement of Anticancer Activity against Cancer Cells
Tao, B., & Yin, Z. (2020) · Polymers · doi:10.3390/polym12051132 · Cited by 34
“Most stimuli‐responsive carriers release drugs by breaking chemical bonds, such as hydrazine [9], oxime [10], azo [11], or disulfide bonds [12].”
Background
Molecular bottlebrush with pH-responsive cleavable bonds as a unimolecular vehicle for anticancer drug delivery
Raj, W., Jerczyński, K., Rahimi, M., Przekora, A., Matyjaszewski, K. A., & Pietrasik, J. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112439 · Cited by 34
Non-Viral Carriers for Nucleic Acids Delivery: Fundamentals and Current Applications
Shtykalova, S., Deviatkin, D., Freund, S., Egorova, A., & Kiselev, A. (2023) · Life · doi:10.3390/life13040903 · Cited by 43
“It should be noted that any of the described mechanisms of endosomal escape may turn out to be sensitive to different modifications, especially those that aim at surface modifications and increase circulation time [92].”
Background
pH and thermo dual-responsive starch-g-P(DEAEMA-co-PEGMA): Synthesis via SET-LRP, self-assembly and drug release behaviors
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Nazli, A., Khan, M. Z. I., Rácz, Á., & Béni, S. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116699 · Cited by 38
Platinum nanoparticles in cancer therapy: chemotherapeutic enhancement and ROS generation
Faderin, E., Iorkula, T. H., Aworinde, O. R., Awoyemi, R. F., Awoyemi, C. T., Acheampong, E., Agyemang, P., Onaiwu, G. E., & Ifijen, I. H. (2025) · Medical Oncology · doi:10.1007/s12032-024-02598-w · Cited by 35
DNA-Based nanostructures for tumor microenvironment-responsive drug delivery
Li, S., Xu, M., Yao, C., & Yang, D. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115610 · Cited by 34
pH-Sensitive PEGylated liposomes for delivery of an acidic dinitrobenzamide mustard prodrug: Pathways of internalization, cellular trafficking and cytotoxicity to cancer cells
Yang, M. M., Wilson, W. R., & Wu, Z. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.11.041 · Cited by 33
Self-citation
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Salar, S., Mehrnejad, F., Sajedi, R. H., & Arough, J. M. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.05.140 · Cited by 33
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Mehtani, D., Seth, A., Sharma, P. A., Maheshwari, N., Kapoor, D. U., Shrivastava, S. K., & Tekade, R. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814427-5.00004-4 · Cited by 36
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“5 [9], so the response of the nanoparticle to such acidic conditions would be useful towards endosomal escape and targeted drug release [9,24].”
Background
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Li, C., Wang, Y., Jiang, H., & Wang, X. (2020) · Journal of The Electrochemical Society · doi:10.1149/1945-7111/ab67a3 · Cited by 33
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Agazzi, M. L., Herrera, S. E., Cortez, M. L., Marmisollé, W. A., & Azzaroni, O. (2020) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2020.110895 · Cited by 33
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Liu, C., Liu, Q., Chen, L., Li, M., Yin, J., Zhu, X., & Chen, D. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000899 · Cited by 33
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Li, W., Li, M., & Qi, J. (2021) · Molecules · doi:10.3390/molecules26185567 · Cited by 34
“0 [44]; (2) tumor cells present a reductive environment in which glutathione concentration can reach 1–10 mM, which is 100–1000 times than that of the blood environment [45]; (3) mitochondria of tumor cells present an oxidative environment, in which the concentration of reactive oxygen species (ROS) can reach mM level…”
Background
Folic acid-conjugated pH-responsive poly(methacrylic acid) nanospheres for targeted delivery of anticancer drugs to breast cancer cells
Ghalehkhondabi, V., Fazlali, A., & Soleymani, M. (2021) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2021.118028 · Cited by 33
Design of Organic Macrocycle‐Modified Iron Oxide Nanoparticles for Drug Delivery
Škorjanc, T., Benyettou, F., Olsen, J., & Trabolsi, A. (2017) · Chemistry - A European Journal · doi:10.1002/chem.201605246 · Cited by 33
Advance Progress in Assembly Mechanisms of Carrier-Free Nanodrugs for Cancer Treatment
Zhang, X., Hu, S., Huang, L., Chen, X., Wang, X., Fu, Y., Sun, H. J., Li, G., & Wang, X. (2023) · Molecules · doi:10.3390/molecules28207065 · Cited by 37
“The transmembrane pH gradient varies in different subcellular components, such as mitochondria for pH 8.0, endosomes for pH 5.6–6.0, and lysosomes for pH 4.5–5.0 [89,90].”
BackgroundInfluential
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Xu, D., Guo, D., Zhang, J., Tan, X., Deng, Z., Hou, X., & Wang, S. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124145 · Cited by 32
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Ramakrishnan, P., Ramakrishnan, R., Jalaludeen, A. M., Jayakumar, R., Gimbun, J., Ranganathan, B., Mohamed, S. B., Sridhar, T. M., Gunasekaran, S. S., MubarakAli, D., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139663 · Cited by 32
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Liu, Z., Gao, Y., Shao, W., Guo, X., Zhao, D., Yang, R., & Li, S. (2025) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37952 · Cited by 34
Fabrication of ultrathin nanocellulose shells on tough microparticles via an emulsion-templated colloidal assembly: towards versatile carrier materials
Fujisawa, S., Togawa, E., Kuroda, K., Saito, T., & Isogai, A. (2019) · Nanoscale · doi:10.1039/c9nr02612f · Cited by 32
Next Generation Nanomaterials: Smart Nanomaterials, Significance, and Biomedical Applications
Thangudu, S. (2020) · Springer eBooks · doi:10.1007/978-981-15-4802-4_15 · Cited by 35
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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery
Hughes, K. A., Misra, B., Maghareh, M., & Bobbala, S. K. R. (2023) · Nano Research · doi:10.1007/s12274-022-5267-5 · Cited by 31
Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline Adjuvants
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Authors: Kanamala, M., Wilson, W. R., Yang, M., Palmer, B. D., & Wu, Z.
Affiliations: University of Auckland (NZ)
Corresponding author: Wu, Zimei
ORCID: Wilson, William R.
Yang, Mimi
Wu, Zimei
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2016-04
Volume: 85
Pages: 152-167
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2016.01.061
OpenAlex: W2288119981
Cited by: 1,004
References: 213
Citations by year: 2026: 65 · 2025: 96 · 2024: 78 · 2023: 85 · 2022: 99 · 2021: 117 · 2020: 129 · 2019: 113 · 2018: 108 · 2017: 77 · 2016: 37
FWCI: 5.98
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biomaterials (publishedVersion)
PubMed (publishedVersion)
ResearchSpace (University of Auckland) (submittedVersion)
Funders: Royal Society of New Zealand (UOA1201)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords: pH-responsive nanocarriers, tumour-targeted drug delivery, stimuli-responsive drug release, intracellular drug release, protonation, charge reversal, bond cleavage, tumor selectivity, multidrug resistance, chemotherapy
MeSH terms: Animals, Biocompatible Materials, Clinical Trials as Topic, Disease Models, Animal, Humans, Hydrogen-Ion Concentration, Neoplasms, Drug Delivery Systems, Nanotechnology, Nanostructures, Drug Liberation

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Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review

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