Smart Nanovesicle-Mediated Immunogenic Cell Death through Tumor Microenvironment Modulation for Effective Photodynamic Immunotherapy.

Abstract

Combination therapy that could better balance immune activation and suppressive signals holds great potential in cancer immunotherapy. Herein, we serendipitously found that the pH-responsive nanovesicles (pRNVs) self-assembled from block copolymer polyethylene glycol-b-cationic polypeptide can not only serve as a nanocarrier but also cause immunogenic cell death (ICD) through preapoptotic exposure of calreticulin. After coencapsulation of a photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) and an indoleamine 2,3-dioxygenase inhibitor, indoximod (IND), pRNVs/HPPH/IND at a single low dose elicited significant antitumor efficacy and abscopal effect following laser irradiation in a B16F10 melanoma tumor model. Treatment efficacy attributes to three key factors: (i) singlet oxygen generation by HPPH-mediated photodynamic therapy (PDT); (ii) increased dendritic cell (DC) recruitment and immune response provocation after ICD induced by pRNVs and PDT; and (iii) tumor microenvironment modulation by IND via enhancing P-S6K phosphorylation for CD8+ T cell development. This study exploited the nanocarrier to induce ICD for the host's immunity activation. The "all-in-one" smart nanovesicles allow the design of multifunctional materials to strengthen cancer immunotherapy efficacy.

• Authors: Weijing Yang, Fuwu Zhang, Hongzhang Deng, Lisen Lin, Sheng Wang, Fei Kang, Guocan Yu, Joseph Lau, Rui Tian, Mingru Zhang, Zhantong Wang, Liangcan He, Ying Ma, Gang Niu, Shuo Hu, Xiaoyuan Chen
• Journal: ACS nano (ACS Nano) Vol. 14 Issue 1 Pg. 620-631 (01 28 2020) ISSN: 1936-086X [Electronic] United States
• PMID: 31877023 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Peptides
• Photosensitizing Agents
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Drug Carriers (chemistry, pharmacology)
• Hydrogen-Ion Concentration
• Immunogenic Cell Death (drug effects, immunology)
• Immunotherapy
• Melanoma (immunology, pathology, therapy)
• Mice
• Molecular Structure
• Nanoparticles (chemistry)
• Particle Size
• Peptides (chemistry, pharmacology)
• Photochemotherapy
• Photosensitizing Agents (chemistry, pharmacology)
• Polyethylene Glycols (chemistry, pharmacology)
• Surface Properties
• Tumor Microenvironment (drug effects, immunology)