2. Academic Validation
  3. Drug-drug conjugates self-assembled nanomedicines triggered photo-/immuno- therapy for synergistic cancer treatments

Drug-drug conjugates self-assembled nanomedicines triggered photo-/immuno- therapy for synergistic cancer treatments

  • J Control Release. 2023 Sep 28:363:361-375. doi: 10.1016/j.jconrel.2023.09.042.
Haijing Qu 1,  Longmeng Li 2,  Han Chen 1,  Menghuan Tang 2,  Wei Cheng 1,  Tzu-Yin Lin 3,  Lingyan Li 4,  Bin Li 5,  Xiangdong Xue 6
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 2 Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA.
  • 3 Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA.
  • 4 Alphacait AI Biotech ch., LTD, No.10, Xixi Wetland, Wuchang Ave, Hangzhou, Zhejiang 310023, China.
  • 5 Alphacait AI Biotech ch., LTD, No.10, Xixi Wetland, Wuchang Ave, Hangzhou, Zhejiang 310023, China. Electronic address: binli@alphacait.com.
  • 6 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: xuexd@sjtu.edu.cn.
PMID: 37751826 DOI: 10.1016/j.jconrel.2023.09.042
Abstract

Although immunotherapies have made progress in Cancer treatment, their clinical response rates vary widely and are typically low due to sparse immune cell infiltration (immune "cold") and suppressive tumor immune microenvironment (TIME). A simple yet effective approach that integrates a variety of immune-stimulating and TIME-modulating functions could potentially address this clinical challenge. Herein, we conjugate two small molecules, including a photosensitizer (pyropheophorbide-a, PA) and a Toll-like Receptor 7/8 agonist (resiquimod, R848), into prodrug (PA-R848) that self-assembles into PA-R848 esterase responsive nanoparticles (PARE NPs) with 100% drug composition and synergistic photo-/immune- therapeutic effects. In PARE NPs, PA exhibits strong phototherapeutic effects which ablate the primary tumor directly and elicits immunogenic cell death (ICD) to promote the immune response. R848 effectively polarizes the M2-type tumor-associated macrophage (TAM) to M1-type TAM, consequently reversing the "cold" and suppressive TIME when working together with phototherapy. The PARE NPs can efficiently pare down the tumor development by two synergisms, including i) synergistic immunotherapy between ICD and TAM polarization; ii) and the antitumor effects between phototherapy and immunotherapy. On a head-neck squamous cell carcinoma mouse model, PARE NPs combined with PD-1 antibody eliminate primary tumors, and significantly inhibit the progress of distant tumors thanks to the robust antitumor immunity enhanced by the PARE NPs.

Keywords

Immune responses; Immunotherapy; Nanomedicine; Phototherapy.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z