Endogenous PH-responsive Nanoparticles with Programmable Size Changes for Targeted Tumor Therapy and Imaging Applications

Overview

Journal Theranostics

Date 2018 Jun 14

PMID 29896301

Citations 64

Authors

Wei Wu

Li Luo

Yi Wang

Qi Wu

Han-Bin Dai

Jian-Shu Li

Colm Durkan

Nan Wang

Gui-Xue Wang

Affiliations

Soon will be listed here.

Abstract

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed.

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References

Wilson J, Keller S, Manganiello M, Cheng C, Lee C, Opara C . pH-Responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. ACS Nano. 2013; 7(5):3912-25. PMC: 4042837. DOI: 10.1021/nn305466z. View

Huang X, Brazel C . On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001; 73(2-3):121-36. DOI: 10.1016/s0168-3659(01)00248-6. View

Li Y, Zhao T, Wang C, Lin Z, Huang G, Sumer B . Molecular basis of cooperativity in pH-triggered supramolecular self-assembly. Nat Commun. 2016; 7:13214. PMC: 5095283. DOI: 10.1038/ncomms13214. View

King M, Mohamed Z . Dual nanoparticle drug delivery: the future of anticancer therapies?. Nanomedicine (Lond). 2016; 12(2):95-98. DOI: 10.2217/nnm-2016-0378. View

Meng F, Zhong Y, Cheng R, Deng C, Zhong Z . pH-sensitive polymeric nanoparticles for tumor-targeting doxorubicin delivery: concept and recent advances. Nanomedicine (Lond). 2014; 9(3):487-99. DOI: 10.2217/nnm.13.212. View

Nowacek A, Balkundi S, McMillan J, Roy U, Martinez-Skinner A, Mosley R . Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages. J Control Release. 2010; 150(2):204-11. PMC: 3065529. DOI: 10.1016/j.jconrel.2010.11.019. View

Song C, Ji R, Du F, Liang D, Li Z . Oxidation-Accelerated Hydrolysis of the Ortho Ester-Containing Acid-Labile Polymers. ACS Macro Lett. 2022; 2(3):273-277. DOI: 10.1021/mz4000392. View

Jhaveri A, Deshpande P, Torchilin V . Stimuli-sensitive nanopreparations for combination cancer therapy. J Control Release. 2014; 190:352-70. DOI: 10.1016/j.jconrel.2014.05.002. View

Liu X, Chen Y, Li H, Huang N, Jin Q, Ren K . Enhanced retention and cellular uptake of nanoparticles in tumors by controlling their aggregation behavior. ACS Nano. 2013; 7(7):6244-57. DOI: 10.1021/nn402201w. View

10.

Lynn D, Amiji M, Langer R . pH-Responsive Polymer Microspheres: Rapid Release of Encapsulated Material within the Range of Intracellular pH Financial support was provided by the NSF (Cooperative Agreement No. ECC9843342 to the MIT Biotechnology Process Engineering Center), the.... Angew Chem Int Ed Engl. 2001; 40(9):1707-1710. View

11.

Wang C, Wang Y, Li Y, Bodemann B, Zhao T, Ma X . A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles. Nat Commun. 2015; 6:8524. PMC: 4600749. DOI: 10.1038/ncomms9524. View

12.

Sosnik A, Menaker Raskin M . Polymeric micelles in mucosal drug delivery: Challenges towards clinical translation. Biotechnol Adv. 2015; 33(6 Pt 3):1380-92. DOI: 10.1016/j.biotechadv.2015.01.003. View

13.

Hou W, Zhao X, Qian X, Pan F, Zhang C, Yang Y . pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy. Nanoscale. 2015; 8(1):104-16. DOI: 10.1039/c5nr06842h. View

14.

Tang S, Yin Q, Su J, Sun H, Meng Q, Chen Y . Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (β-amino ester) nanoparticles co-delivering two siRNA and paclitaxel. Biomaterials. 2015; 48:1-15. DOI: 10.1016/j.biomaterials.2015.01.049. View

15.

Dai Y, Ma P, Cheng Z, Kang X, Zhang X, Hou Z . Up-conversion cell imaging and pH-induced thermally controlled drug release from NaYF4/Yb3+/Er3+@hydrogel core-shell hybrid microspheres. ACS Nano. 2012; 6(4):3327-38. DOI: 10.1021/nn300303q. View

16.

Subramanian A, Manigandan A, Sivashankari P, Sethuraman S . Development of nanotheranostics against metastatic breast cancer--A focus on the biology & mechanistic approaches. Biotechnol Adv. 2015; 33(8):1897-911. DOI: 10.1016/j.biotechadv.2015.10.002. View

17.

Zhao T, Huang G, Li Y, Yang S, Ramezani S, Lin Z . A Transistor-like pH Nanoprobe for Tumour Detection and Image-guided Surgery. Nat Biomed Eng. 2017; 1. PMC: 5617128. DOI: 10.1038/s41551-016-0006. View

18.

Chen Y, Ai K, Liu J, Sun G, Yin Q, Lu L . Multifunctional envelope-type mesoporous silica nanoparticles for pH-responsive drug delivery and magnetic resonance imaging. Biomaterials. 2015; 60:111-20. DOI: 10.1016/j.biomaterials.2015.05.003. View

19.

Huang P, Song H, Wang W, Sun Y, Zhou J, Wang X . Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor. Biomacromolecules. 2014; 15(8):3128-38. DOI: 10.1021/bm500764p. View

20.

Vila-Caballer M, Codolo G, Munari F, Malfanti A, Fassan M, Rugge M . A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: An application for bladder cancer treatment. J Control Release. 2016; 238:31-42. DOI: 10.1016/j.jconrel.2016.07.024. View