Photodynamic Therapy Combined with Antihypoxic Signaling and CpG Adjuvant as an In Situ Tumor Vaccine Based on Metal–Organic Framework Nanoparticles to Boost Cancer Immunotherapy

Abstract

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT‐induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal–organic framework (MOF)‐based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF‐based nanoparticles are self‐assembled from H2TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN‐ACF‐CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF‐1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT‐based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune‐responses both in vitro and in vivo, which may have great potential for clinical translation in future.

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…Importantly, this inexpensive HA nanoparticle-based delivery system could enhance the bioavailability of CpG ODNs and reduce the risk of side effects caused by positively-charged cationic lipids, which made these adjuvant-loaded nanomedicines safer and more affordable for cancer immunotherapy. In addition to delivering CpG ODN with Poly I: C, in another recent study [ 258 ], HA-based nanoparticles were employed to load CpG along with another therapeutic hypoxia inducible factor: signaling inhibitor Acriflavine (ACF) [ [259] , [260] , [261] ]. In this study, HA coated metal–organic framework-based nanoparticles were synthesized through H2TCPP and zirconium ions as a delivery platform (PCN-ACF-CpG@HA).…”

Immunogenic Cell Death-Based Cancer Vaccines

“…The modified oxygen-boosted PDT displayed infiltration of cytotoxic T lymphocytes (CTLs) in TME and a better induction of ICD in 4T1 murine breast cancer cells by elevating cell surface exposure of CRT, increasing release of HMGB1 and ATP, and afterwards promoting the maturation of DCs ( 57 ). Combing metal-organic framework-based nanoparticles to PDT was also of benefit for alleviating PDT-induced hypoxia via inhibiting hypoxia inducible factor-1α ( 59 ). The combination of nanomaterials or anti-hypoxic treatment with PDT may help it to achieve a better clinical realization.…”

Recent Advances in Nanoscale Metal–Organic Frameworks Towards Cancer Cell Cytotoxicity: An Overview

“…To counter this phenomenon, Cai et al . [ 78 ] developed a similar photosensitive MOF (denoted PCN-ACF-CpG@HA, Fig. 17 b) to that of Ni et al .…”