Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 24, Pages 6253-6258Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201311227
Keywords
antitumor agents; drug delivery; nanogels; pH responsive; tumor penetration
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Funding
- National Natural Science Foundation of China [81072589, 81273468]
- State Key Laboratory of Natural Medicines at China Pharmaceutical University [SKLNMZZ201206, SKLNMZZCX201306]
- 111 Project from the Ministry of Education of China and the State Administration of Foreign Expert Affairs of China [111-2-07]
- Fundamental Research Funds for the Central Universities [2410698]
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To achieve deep tumor penetration of large-sized nanoparticles (NPs), we have developed a reversible swelling-shrinking nanogel in response to pH variation for a sequential intra-intercellular NP delivery. The nanogel had a crosslinked polyelectrolyte core, consisting of N-lysinal-N'-succinyl chitosan and poly(N-isopropylacrylamide), and a crosslinked bovine serum albumin shell, which was able to swell in an acidic environment and shrink back under neutral conditions. The swelling resulted in a rapid release of the encapsulated chemotherapeutics in the cancer cells for efficient cytotoxicity. After being liberated from the dead cells, the contractive nanogel could infect neighboring cancer cells closer to the center of the tumor tissue.
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