Houliang Tang


Biodegradable ultra-pH sensitive (UPS) copolymers were prepared in the presence of a cyclic ketene acetal, 2-methylene-4-phenyl-1,3-dioxolane (MPDL), as a comonomer for the atom transfer radical polymerization (ATRP) of acrylic monomers. Due to the incorporation of ester linkages in the polymer backbone, the new nanoprobes were prone to hydrolysis and can be degraded into non-cytotoxic compounds. Meantime, with a number of ionizable tertiary amine side groups, the synthesized block copolymers displayed varied hydrophilicity at different pHs. A slight pH decrease could lead to a rapid dissociation of the micelles into unimers, resulting in the release of entrapped drug or the activation of suppressed fluorophores. The detailed polymer synthesis, ultra-pH sensitivity and degradation of the new UPS nanoprobes will be discussed in this study.

Keywords: ultra-pH sensitive, micelle, tumour imaging, drug delivery, degradation, cyclic ketene acetal, ATRP.



Roy D, Cambre JN, Sumerlin BS, Future perspectives and recent advances in stimuli-responsive materials, Progress in Polymer Science, 2010; 35(1):278-301.

De las Heras Alarcón C, Pennadam S, Alexander C, Stimuli responsive polymers for biomedical applications, Chemical Society Reviews, 2005; 34(3):276-285.

Wang Z, Luo M, Mao C, Wei Q, Zhao T, Li Y, Huang G, Gao J, A redox‐activatable fluorescent sensor for the high‐throughput quantification of cytosolic delivery of macromolecules, Angewandte Chemie, 2017; 129(5):1339-1343.

So MK, Xu C, Loening AM, Gambhir SS, Rao J, Self-illuminating quantum dot conjugates for in vivo imaging, Nature biotechnology, 2006; 24(3):339-343.

Gu L, Mooney DJ, Biomaterials and emerging anticancer therapeutics: engineering the microenvironment, Nature reviews. Cancer, 2016; 16(1):56-66.

Kwee BJ, Mooney DJ, Biomaterials for skeletal muscle tissue engineering, Current Opinion in Biotechnology, 2017; 47:16-22.

Mura S, Nicolas J, Couvreur P, Stimuli-responsive nanocarriers for drug delivery, Nature materials, 2013; 12(11):991-1003.

Demaurex N, pH Homeostasis of cellular organelles, Physiology, 2002; 17(1):1-5.

Vander Heiden MG, Cantley LC, Thompson CB, Understanding the Warburg effect: the metabolic requirements of cell proliferation, Science, 2009; 324(5930):1029-1033.

Webb BA, Chimenti M, Jacobson MP, Barber DL, Dysregulated pH: a perfect storm for cancer progression, Nature reviews. Cancer, 2011; 11(9):671-677.

Hanahan D, Weinberg RA, Hallmarks of cancer: the next generation, Cell, 2011; 144(5):646-674.

Schmaljohann D, Thermo-and pH-responsive polymers in drug delivery, Advanced drug delivery reviews, 2006; 58(15):1655-1670.

Kocak G, Tuncer C, Bütün V, pH-Responsive polymers, Polymer Chemistry, 2017; 8(1):144-176.

Dai S, Ravi P, Tam KC, pH-Responsive polymers: synthesis, properties and applications, Soft Matter, 2008; 4(3):435-449.

Lu Y, Sun W, Gu Z, Stimuli-responsive nanomaterials for therapeutic protein delivery, Journal of Controlled Release, 2014,;194:1-9.

Wang Y, Zhou K, Huang G, Hensley C, Huang X, Ma X, Zhao T, Sumer BD, DeBerardinis RJ, Gao J, A broad nanoparticle-based strategy for tumor imaging by nonlinear amplification of microenvironment signals, Nature materials, 2014; 13(2):204-212.

Wang C, Wang Y, Li Y, Bodemann B, Zhao T, Ma X, Huang G, Hu Z, DeBerardinis RJ, White MA, Gao J, A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles, Nature communications, 2015; 6:8524-8534.

Li Y, Zhao T, Wang C, Lin Z, Huang G, Sumer BD, Gao J, Molecular basis of cooperativity in pH-triggered supramolecular self-assembly, Nature communications, 2016; 7:13214-13224.

Li Y, Wang Z, Wei Q, Luo M, Huang G, Sumer BD, Gao J, Non-covalent interactions in controlling pH-responsive behaviors of self-assembled nanosystems, Polymer Chemistry, 2016; 7(38):5949-5956.

Li Y, Wang Y, Huang G, Ma X, Zhou K, Gao J, Chaotropic‐anion‐induced supramolecular self‐assembly of ionic polymeric micelles, Angewandte Chemie International Edition, 2014; 53(31):8074-8078.

Kumari A, Yadav SK, Yadav SC, Biodegradable polymeric nanoparticles based drug delivery systems, Colloids and Surfaces B: Biointerfaces, 2010; 75(1):1-8.

Zhao W, Xu Z, Cui Q, Sahai N, Predicting the structure–activity relationship of hydroxyapatite-binding peptides by enhanced-sampling molecular simulation, Langmuir, 2016; 32(27):7009-7022..

Tang H, Tsarevsky NV, Preparation and functionalization of linear and reductively degradable highly branched cyanoacrylate‐based polymers, Journal of Polymer Science Part A: Polymer Chemistry, 2016; 54(23):3683-3693.

Agarwal S, Chemistry, chances and limitations of the radical ring-opening polymerization of cyclic ketene acetals for the synthesis of degradable polyesters, Polymer Chemistry, 2010; 1(7):953-964.

Tang H, Tsarevsky NV, Lipoates as building blocks of sulfur-containing branched macromolecules, Polymer Chemistry, 2015; 6(39):6936-6945.

Zhou K, Wang Y, Huang X, Luby‐Phelps K, Sumer BD, Gao J, Tunable, ultrasensitive pH‐responsive nanoparticles targeting specific endocytic organelles in living cells, Angewandte Chemie, 2011; 123(27): 6233-6238.

Bronstein LM, Sidorov SN, Zhirov V, Zhirov D, Kabachii YA, Kochev SY, Valetsky PM, Stein B, Kiseleva OI, Polyakov SN, Shtykova EV, Metalated diblock and triblock poly (ethylene oxide)-block-poly (4-vinylpyridine) copolymers: Understanding of micelle and bulk structure, The Journal of Physical Chemistry B, 2005; 109(40):18786-18798.

Tran J, Guégain E, Ibrahim N, Harrisson S, Nicolas J, Efficient synthesis of 2-methylene-4-phenyl-1, 3-dioxolane, a cyclic ketene acetal for controlling the NMP of methyl methacrylate and conferring tunable degradability, Polymer Chemistry, 2016; 7(26):4427-4435.

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