Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles

Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles

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 nons...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 7; pp. 1 - 8
Main Authors: Hu, Jamie K., Suh, Hee-Won, Qureshi, Munibah, Lewis, Julia M., Yaqoob, Sharon, Moscato, Zoe M., Griff, Sofia, Lee, Alison K., Yin, Emily S., Saltzman, W. Mark, Girardi, Michael
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 16-02-2021
Series:From the Cover
Subjects:
Aldehydes
Biodegradability
Biodegradation
Biological Sciences
Bonding strength
Camptothecin
Cancer
Covalent bonds
CpG islands
Diols
Drug delivery
Drug delivery systems
Immunostimulation
Immunotherapy
Malignancy
Nanoparticles
Oligonucleotides
Physical Sciences
Polyglycerols
Polylactic acid
Polymers
Skin cancer
Squamous cell carcinoma
Tumors
nanoparticle
drug delivery
chemotherapy
immunotherapy
squamous cell carcinoma
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Summary: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.
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Author contributions: J.K.H., H.-W.S., J.M.L., W.M.S., and M.G. designed research; J.K.H., H.-W.S., M.Q., J.M.L., S.Y., Z.M.M., S.G., A.K.L., and E.S.Y. performed research; J.K.H., H.-W.S., M.Q., J.M.L., S.Y., Z.M.M., S.G., A.K.L., and E.S.Y. analyzed data; and J.K.H., J.M.L., W.M.S., and M.G. wrote the paper.
Edited by Joseph M. DeSimone, Stanford University, Stanford, CA, and approved January 5, 2021 (received for review October 6, 2020)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2020575118