Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy

Xilong Wu; Yundi Wu; Hongbo Ye; Shuangjiang Yu; Chaoliang He; Xuesi Chen

doi:10.1016/j.jconrel.2017.04.011

Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy

J Control Release. 2017 Jun 10:255:81-93. doi: 10.1016/j.jconrel.2017.04.011. Epub 2017 Apr 10.

Authors

Xilong Wu¹, Yundi Wu², Hongbo Ye³, Shuangjiang Yu², Chaoliang He⁴, Xuesi Chen⁵

Affiliations

¹ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100039, People's Republic of China.
² Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
³ School of Pharmaceutical Sciences, Jilin University, Changchun 130021, People's Republic of China.
⁴ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China. Electronic address: [email protected].
⁵ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China. Electronic address: [email protected].

PMID: 28408199
DOI: 10.1016/j.jconrel.2017.04.011

Abstract

In situ-forming thermosensitive hydrogels based on poly(ethylene glycol)-poly(γ-ethyl-l-glutamate) diblock copolymers (mPEG-b-PELG) were prepared for the co-delivery of interleukin-15 (IL-15) and cisplatin (CDDP). The polypeptide-based hydrogels as local drug delivery carriers could reduce the systemic toxicity, degrade thoroughly within 3weeks after subcutaneous injection into rats and display an acceptable biocompatibility. When incubated with mouse melanoma B16 cells, only the CDDP-treated groups had significant effects on the S phase cell-cycle arrest in melanoma cells. After a single peritumoral injection of the hydrogel containing IL-15/CDDP in C57BL/6 mice inoculated with B16F0-RFP melanoma cells, the dual drug-loaded hydrogels displayed synergistic anticancer efficacy, which was resulted from a combination of CDDP-mediated S arrest and IL-15/CDDP-induced recovery of CD8⁺ T cell and NK cell populations to reduce immunosuppression and enhance antitumor immunity. Hence, the as-prepared thermosensitive polypeptide hydrogels for localized and sustained co-delivery of IL-15 and CDDP may have potential for efficient treatment of melanoma.

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
CD8-Positive T-Lymphocytes / drug effects
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Cisplatin / administration & dosage*
Cisplatin / chemistry
Cisplatin / pharmacology
Cisplatin / therapeutic use
Cytokines / immunology
Drug Delivery Systems*
Drug Liberation
Hydrogels / administration & dosage*
Hydrogels / chemistry
Hydrogels / pharmacology
Hydrogels / therapeutic use
Interleukin-15 / administration & dosage*
Interleukin-15 / chemistry
Interleukin-15 / pharmacology
Interleukin-15 / therapeutic use
Killer Cells, Natural / drug effects
Male
Melanoma, Experimental / drug therapy
Melanoma, Experimental / immunology
Mice, Inbred C57BL
Peptides / administration & dosage
Peptides / chemistry
Peptides / pharmacology
Peptides / therapeutic use
Polyethylene Glycols / administration & dosage
Polyethylene Glycols / chemistry
Polyethylene Glycols / pharmacology
Polyethylene Glycols / therapeutic use
Rats, Sprague-Dawley

Substances

Antineoplastic Agents
Cytokines
Hydrogels
Interleukin-15
Peptides
Polyethylene Glycols
monomethoxypolyethylene glycol
Cisplatin