title: Near-Infrared-Triggered Photodynamic Therapy with Multitasking Upconversion Nanoparticles in Combination with Checkpoint Blockade for Immunotherapy of Colorectal Cancer.
abstract: While immunotherapy has become a highly promising paradigm for cancer treatment in recent years, it has long been recognized that photodynamic therapy (PDT) has the ability to trigger antitumor immune responses. However, conventional PDT triggered by visible light has limited penetration depth, and its generated immune responses may not be robust enough to eliminate tumors. Herein, upconversion nanoparticles (UCNPs) are simultaneously loaded with chlorin e6 (Ce6), a photosensitizer, and imiquimod (R837), a Toll-like-receptor-7 agonist. The obtained multitasking UCNP-Ce6-R837 nanoparticles under near-infrared (NIR) irradiation with enhanced tissue penetration depth would enable effective photodynamic destruction of tumors to generate a pool of tumor-associated antigens, which in the presence of those R837-containing nanoparticles as the adjuvant are able to promote strong antitumor immune responses. More significantly, PDT with UCNP-Ce6-R837 in combination with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade not only shows excellent efficacy in eliminating tumors exposed to the NIR laser but also results in strong antitumor immunities to inhibit the growth of distant tumors left behind after PDT treatment. Furthermore, such a cancer immunotherapy strategy has a long-term immune memory function to protect treated mice from tumor cell rechallenge. This work presents an immune-stimulating UCNP-based PDT strategy in combination with CTLA-4 checkpoint blockade to effectively destroy primary tumors under light exposure, inhibit distant tumors that can hardly be reached by light, and prevent tumor reoccurrence via the immune memory effect.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Ligeng
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Chenya
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, and ‡School of Biology & Basic Medical Science, Medical College, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Zhuang
authors.identifier: 0000-0002-1629-1039
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000187:drug effects; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D003110:Colonic Neoplasms / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000077271:Imiquimod; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D000077271:Imiquimod
keywords: checkpoint blockade; immune memory; immunotherapy; photodynamic therapy; upconversion nanoparticles