气候变化领域集成服务门户(CCPortal): Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles

CCPortal

DOI	10.1073/pnas.2020575118
	Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles
	Hu J.K.; Suh H.-W.; Qureshi M.; Lewis J.M.; Yaqoob S.; Moscato Z.M.; Griff S.; Lee A.K.; Yin E.S.; Mark Saltzman W.; Girardi M.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	Keratinocyte-derived carcinomas, including squamous cell carcinoma (SCC), comprise the most common malignancies. Surgical excision is the therapeutic standard but is not always clinically feasible, and currently available alternatives are limited to superficial tumors. To address the need for a nonsurgical treatment for nodular skin cancers like SCC, we developed a bioadhesive nanoparticle (BNP) drug delivery system composed of biodegradable polymer, poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are nonadhesive NPs (NNPs), which are stealthy in their native state, but we have previously shown that conversion of the vicinal diols of HPG to aldehydes conferred NPs the ability to form strong covalent bonds with amine-rich surfaces. Herein, we show that these BNPs have significantly enhanced binding to SCC tumor cell surfaces and matrix proteins, thereby significantly enhancing the therapeutic efficacy of intratumoral drug delivery. Tumor injection of BNP-CPT resulted in tumor retention of CPT at ∼50% at 10 d postinjection, while CPT was undetectable in NNP-CPT or free (intralipid) CPT-injected tumors at that time. BNP-CPT also significantly reduced tumor burden, with a portion (∼20%) of BNP-CPT–treated established tumors showing histologic cure. Larger, more fully established PDV SCC tumors treated with a combination of BNP-CPT and immunostimulating CpG oligodeoxynucleotides exhibited enhanced survival relative to controls, revealing the potential for BNP delivery to be used along with local tumor immunotherapy. Taken together, these results indicate that percutaneous delivery of a chemotherapeutic agent via BNPs, with or without adjuvant immunostimulation, represents a viable, nonsurgical alternative for treating cutaneous malignancy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Squamous cell carcinoma \| drug delivery \| nanoparticle \| chemotherapy \| immunotherapy
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180643
作者单位	Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06520, United States; Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT 06511, United States
推荐引用方式 GB/T 7714	Hu J.K.,Suh H.-W.,Qureshi M.,et al. Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles[J],2021,118(7).
APA	Hu J.K..,Suh H.-W..,Qureshi M..,Lewis J.M..,Yaqoob S..,...&Girardi M..(2021).Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Hu J.K.,et al."Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).