Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles
| Autor: | W. Mark Saltzman, Jamie K. Hu, Sharon Yaqoob, Alison K. Lee, Julia M. Lewis, Zoe M. Moscato, Sofia Griff, Michael Girardi, Emily S. Yin, Hee-Won Suh, Munibah Qureshi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Glycerol
endocrine system Skin Neoplasms Polymers CpG Oligodeoxynucleotide Polyesters medicine.medical_treatment Bioadhesive 02 engineering and technology Mice 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Adhesives Cell Line Tumor medicine Animals heterocyclic compounds neoplasms Chemotherapy Multidisciplinary business.industry Immunotherapy 021001 nanoscience & nanotechnology medicine.disease Antineoplastic Agents Phytogenic Mice Inbred C57BL Physical Sciences Drug delivery Carcinoma Squamous Cell Cancer research Nanoparticles Camptothecin Skin cancer 0210 nano-technology business Adjuvant hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2020575118 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|