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A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles

Sun, Jiao, Wang, Yiqing, Zhang, Jiaxing, Wang, Jianhao, Wang, Cheng·2025·Acta Biomaterialia
DOI 10.1016/j.actbio.2025.07.006
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Abstract

The effective accumulation of drugs within tumor tissues is impeded by extracellular barriers, necessitating repeated dosing in cancer therapy. However, repeated dosing can trigger the accelerated blood clearance (ABC) effect, resulting in limited therapeutic efficacy. Herein, in this study, a drug reservoir strategy was proposed to solve this dilemma, using an amphiphilic polymer (LPHF) with tunable hydrophilicity and morphology transformation capabilities. At pH 7.4, LPHF with balanced hydrophilicity can self-assemble into nanoparticles and be loaded with Dox (LPHF@Dox). At pH 6.5, LPHF@Dox with reduced hydrophilicity undergoes an immediate transition from a dispersed state to a deposited state, which can serve as a tumor-specific drug reservoir. Under the weakly acidic tumor microenvironment, the amide with adjacent carboxylic acid groups in LPHF exhibits pH-dependent hydrolysis, leading to a reversion of LPHF to a hydrophilic state and reconstitution into nanoparticles (LPHF@Dox RC ). The resulting LPHF@Dox RC undergoes charge reversal to a positive state, which coordinated with conjugated folic acid, to synergistically improves both the cellular internalization and tumor penetration of LPHF@Dox RC . This intelligent amphiphilic polymer, functioning as a tumor-specific drug reservoir, may provide a new approach for effective cancer treatment. STATEMENT OF SIGNIFICANCE: This study introduces a pH-responsive polymeric nanoparticle (LPHF) that transforms into a tumor-specifi…

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Research works printed but not linked: 61

  1. Ding, 2025, Self-adaptive nanocarriers overcome multiple physiological barriers to boosting chemotherapy of orthotopic pancreatic cancer, ACS Nano, 19, 662, 10.1021/acsnano.4c11514 · DOI
  2. Li, 2019, TACMAA chemistry-based tumor extracellular pH-responsive polymeric nanomaterials for drug delivery, Acta Polym. Sin., 50, 567
  3. He, 2014, Recent development of poly (Ethylene Glycol)-cholesterol conjugates as drug delivery systems, Int. J. Pharm., 469, 168, 10.1016/j.ijpharm.2014.04.056 · DOI
  4. Peppas, 1999, Poly(Ethylene Glycol)-containing hydrogels in drug delivery, J. Control. Release, 62, 81, 10.1016/S0168-3659(99)00027-9 · DOI
  5. Eguchi, 2023, Pre-treatment of oncolytic reovirus improves tumor accumulation and intratumoral distribution of PEG-liposomes, J. Control. Release, 354, 35, 10.1016/j.jconrel.2022.12.050 · DOI
  6. Bholakant, 2021, Multi-functional polymeric micelles for chemotherapy-based combined cancer therapy, J. Mater. Chem. B, 9, 8718, 10.1039/D1TB01771C · DOI
  7. Zhu, 2023, Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells, J. Adv. Res., 49, 159, 10.1016/j.jare.2022.09.007 · DOI
  8. Xiang, 2024, Nitric oxide-based nanomedicines for conquering TME fortress: say “NO” to insufficient tumor treatment, Adv. Funct. Mater., 34, 10.1002/adfm.202312092 · DOI
  9. Li, 2023, Tumour-microenvironment-responsive Na2S2O8 nanocrystals encapsulated in bollow organosilica-metal-phenolic networks for cycling persistent Tumour-dynamic therapy, Exploration, 4, 10.1002/EXP.20230054 · DOI
  10. Jiang, 2022, Tumor hijacks macrophages and microbiota through extracellular vesicles, Exploration, 2, 10.1002/EXP.20210144 · DOI
  11. Lei, 2023, Understanding and targeting resistance mechanisms in cancer, MedComm. (2020), 4, e265, 10.1002/mco2.265 · DOI
  12. Liu, 2023, “Y-type” PEG modified liposomes could eliminate the accelerated blood clearance (ABC) phenomenon and improved tumor therapy, Appl. Mater. Today, 32
  13. Abu-Dief, 2022, A higher dose of PEGylated gold nanoparticles reduces the accelerated blood clearance phenomenon effect and induces spleen B lymphocytes in albino mice, Histochem. Cell Biol., 157, 641, 10.1007/s00418-022-02086-0 · DOI
  14. He, 2014, Recent development of poly(Ethylene Glycol)-cholesterol conjugates as drug delivery systems, Int. J. Pharm., 469, 168, 10.1016/j.ijpharm.2014.04.056 · DOI
  15. Bao, 2021, The fate of nanoparticles in vivo and the strategy of designing stealth nanoparticle for drug delivery, Curr. Drug Targets, 22, 922, 10.2174/1389450122666210118105122 · DOI
  16. Zhang, 2021, Surface loading of nanoparticles on engineered or natural erythrocytes for prolonged circulation time: strategies and applications, Acta Pharmacol. Sin., 42, 1040, 10.1038/s41401-020-00606-z · DOI
  17. Wu, 2020, Engineering stem cell derived biomimetic vesicles for versatility and effective targeted delivery, Adv. Funct. Mater., 30, 10.1002/adfm.202006169 · DOI
  18. Ma, 2021, Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy, Adv. Mater., 33, 10.1002/adma.202104504 · DOI
  19. Qin, 2022, Bacteria-elicited specific thrombosis utilizing acid-induced cytolysin A expression to enable potent tumor therapy, Adv. Sci., 9, 10.1002/advs.202105086 · DOI
  20. Thrash, 1991, Effect of divalent ions on protein precipitation with polyethylene glycol: mechanism of action and applications, Protein Expr. Purif., 2, 83, 10.1016/1046-5928(91)90015-B · DOI
  21. Roland, 2023, Isoelectric point (PI)-based phase separation (PI-BPS) purification of elastin-like polypeptides (ELPs) containing charged, biologically active fusion proteins (ELP-FPs), Biotechnol. Prog., 39, e3381, 10.1002/btpr.3381 · DOI
  22. Qi, 2004, Novel isoelectric precipitation of proteins in A pressurized carbon dioxide-water-ethanol system, Biotechnol. Prog., 20, 1176, 10.1021/bp0343099 · DOI
  23. Tian, 2022, Co-precipitates proteins prepared by soy and wheat: structural characterisation and functional properties, Int. J. Biol. Macromol., 212, 536, 10.1016/j.ijbiomac.2022.05.149 · DOI
  24. Liu, 2024, Chitooligosaccharide assisted in the construction of pickering high internal phase emulsion near the isoelectric point of porcine plasma protein, Lwt-Food Sci. Technol., 198, 10.1016/j.lwt.2024.116032 · DOI
  25. Wang, 2022, Acid-sensing ion channel 1: potential therapeutic target for tumor, Biomed. Pharmacother., 155, 10.1016/j.biopha.2022.113835 · DOI
  26. Li, 2022, Tumor acid microenvironment-activated self-targeting & aplitting gold nanoassembly for Tumor chemo-radiotherapy, Bioact. Mater., 7, 377
  27. Liu, 2022, A transistor-like pH-sensitive nanodetergent for selective cancer therapy, Nat. Nanotechnol., 17, 541, 10.1038/s41565-022-01085-5 · DOI
  28. Zhou, 2011, Linear polyethyleneimine-based charge-reversal nanoparticles for nuclear-targeted drug delivery, J. Mater. Chem., 21, 19114, 10.1039/c1jm13576g · DOI
  29. Qiu, 2016, Esterase-activated charge-reversal polymer for fibroblast-exempt cancer gene therapy, Adv. Mater., 28, 10613, 10.1002/adma.201603095 · DOI
  30. Xu, 2007, Targeted charge-reversal nanoparticles for nuclear drug delivery, Angew. Chem.-Int. Edit., 46, 4999, 10.1002/anie.200605254 · DOI
  31. Morris, 1978, Intramolecular nucleophilic and general acid catalysis in the hydrolysis of an amide, J. Chem. Soc. Chem. Commun., 14, 591, 10.1039/c39780000591 · DOI
  32. Karaman, 2014, Design, synthesis, and in vitro kinetics study of atenolol prodrugs for the use in aqueous formulations, Sci. World J., 1
  33. Zhang, 2025, Recombinant collagen microneedles for transdermal delivery of antibacterial copper-DNA nanoparticles to treat skin and soft tissue infections, J. Control. Release, 379, 191, 10.1016/j.jconrel.2025.01.016 · DOI
  34. Yan, 2025, Quasi Fe MIL-53 nanozyme inducing ferroptosis and immunogenic cell death for cancer immunotherapy, Nat. Commun., 16, 2290, 10.1038/s41467-025-57542-x · DOI
  35. Li, 2015, Effect of synthesis conditions on physiochemical properties of lauric acid coated superparamagnetic iron oxide nanoparticles, IEEE Trans. Magn., 51, 10.1109/TMAG.2015.2451693 · DOI
  36. Mamani, 2013, Synthesis and characterization of magnetite nanoparticles coated with lauric acid, Mater. Charact., 81, 28, 10.1016/j.matchar.2013.04.001 · DOI · Paper page
  37. Chantadee, 2020, Vancomycin HCl-loaded lauric acid in situ-forming gel with phase inversion for periodontitis treatment, J. Drug Deliv. Sci. Technol., 57, 56247
  38. Su, 2017, Dextran-G-lauric acid as IKK complex inhibitor carrier, RSC Adv., 7, 56247, 10.1039/C7RA04544A · DOI
  39. Delyanee, 2018, Modification of electrospun poly(L-lactic acid)/polyethylenimine nanofibrous scaffolds for biomedical application, Int. J. Polym. Mater. Polym. Biomater., 67, 247, 10.1080/00914037.2017.1320661 · DOI
  40. Xia, 2013, Dually stimuli-responsive hyperbranched polyethylenimine with LCST transition based on hydrophilic-hydrophobic balance, J. Appl. Polym. Sci., 127, 3249, 10.1002/app.37743 · DOI
  41. Jin, 2023, A novel fluorinated polyethyleneimine with MicroRNA-942-5p-sponges polyplex gene delivery system for non-small-cell lung cancer therapy, J. Colloid Interface Sci., 648, 287, 10.1016/j.jcis.2023.05.153 · DOI
  42. Wu, 2021, “Building-block crosslinking” micelles for enhancing cellular transfection of biocompatible polycations, Sci. China-Mater., 64, 241, 10.1007/s40843-020-1366-2 · DOI
  43. Godbey, 1999, Improved packing of poly(Ethylenimine)/DNA complexes increases transfection efficiency, Gene Ther., 6, 1380, 10.1038/sj.gt.3300976 · DOI
  44. Ma, 2025, Synthesis of isoluminol derivatives with A terminal carboxyl group for protein labelling, RSC Adv., 15, 17776, 10.1039/D5RA00677E · DOI
  45. Pergande, 2017, Isoelectric point separations of peptides and proteins, Proteomes, 5, 4, 10.3390/proteomes5010004 · DOI
  46. Carugo, 2007, Isoelectric points of multi-domain proteins, Bioinformation, 2, 101, 10.6026/97320630002101 · DOI
  47. Ząbczyk, 2024, Novel factors affecting fibrin clot formation and their clinical implications, Polish Arch. Intern. Med.-Polskie Arch. Med., 134
  48. Veider, 2024, Charge-reversible nanoparticles: advanced delivery systems for therapy and diagnosis, Small, 20, 10.1002/smll.202304713 · DOI
  49. Zhang, 2022, Charge reversal nano-systems for tumor therapy, J. Nanobiotechnol., 20, 31, 10.1186/s12951-021-01221-8 · DOI
  50. Liang, 2024, Charge-reversal nano-drug delivery systems in the tumor microenvironment: mechanisms, challenges, and therapeutic applications, Int. J. Mol. Sci., 25, 9779, 10.3390/ijms25189779 · DOI
  51. Wu, 2022, Selective enhancing blood flow in solid tumor tissue is the key for achieving satisfactory delivery and therapeutic outcome of nanodrugs via the EPR effect, J. Pers. Med., 12, 1802, 10.3390/jpm12111802 · DOI
  52. Yang, 2019, Role of charge-reversal in the hemo/immuno-compatibility of polycationic gene delivery systems, Acta Biomater., 96, 436, 10.1016/j.actbio.2019.06.043 · DOI
  53. Ozsvári, 2020, A myristoyl amide derivative of doxycycline potently targets cancer stem cells (CSCs) and prevents spontaneous metastasis, without retaining antibiotic activity, Front. Oncol., 10, 10.3389/fonc.2020.01528 · DOI
  54. De Matteis, 2019, Encapsulation of thermo-sensitive lauric acid in silica shell: a green derivate for chemo-thermal therapy in breast cancer cell, Molecules, 24, 2034, 10.3390/molecules24112034 · DOI
  55. Xia, 2018, Folate-targeted selenium nanoparticles deliver therapeutic SiRNA to improve hepatocellular carcinoma therapy, RSC Adv., 8, 25932, 10.1039/C8RA04204G · DOI
  56. Ageev, 2024, Synthesis, biocompatibility and biological bctivity of a graphene oxide-folic acid conjugate for cytarabine delivery, Colloids Surf. A-Physicochem. Eng. Asp., 697, 10.1016/j.colsurfa.2024.134360 · DOI
  57. Pavlenko, 2022, Self-assembly of hydrophobic-amphiphilic diblock copolymers in solution, J. Phys. Condens. Matter, 34, 10.1088/1361-648X/ac462c · DOI
  58. Aliabadi, 2023, Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery, J. Mater. Chem. B, 11, 9325, 10.1039/D3TB01371E · DOI
  59. Jiang, 2018, pH protective Y1 receptor Ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time, Biomaterials, 170, 70, 10.1016/j.biomaterials.2018.04.002 · DOI
  60. Niu, 2012, Controlled synthesis of Shell cross-linked magnetic micelles for efficient liver MR imaging, J. Mater. Chem., 22, 24936, 10.1039/c2jm35308c · DOI
  61. Krivitsky, 2018, Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of SiRNA to tumors, Nanomedicine, 14, 303, 10.1016/j.nano.2017.10.012 · DOI

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Metadata

Authors
Sun, J., Wang, Y., Zhang, J., Wang, J., & Wang, C.
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2025-08
Volume
202
Pages
435-449
ISSN
1742-7061
DOI
10.1016/j.actbio.2025.07.006
Cited by
7
References
0
Language
en
Licence
Funders
  • Graduate Research and Innovation Projects of Jiangsu Province (KYCX23_3033)
  • Soochow University (KJS2104)
  • Jiangsu Provincial Department of Education (21KJD350003)

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CoChat. (2026). Citation check: A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles. https://app.cochat.ai/papers/10.1016/j.actbio.2025.07.006
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Sun, J., Wang, Y., Zhang, J., Wang, J., & Wang, C. (2025). A drug reservoir strategy for long-acting cancer therapy using morphologically transformed amphiphilic polymeric nanoparticles. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2025.07.006