Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity in Osteosarcoma

Namrata Anand; Joseph Robert McCorkle; David S Schweer; Lan Li; Kristen S Hill; Melissa A Fath; Derek B Allison; Christopher L Richards; Jill M Kolesar

doi:10.3390/cells14201616

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Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity in Osteosarcoma

Journal article

Open access

Peer reviewed

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity in Osteosarcoma

Namrata Anand, Joseph Robert McCorkle, David S Schweer, Lan Li, Kristen S Hill, Melissa A Fath, Derek B Allison, Christopher L Richards and Jill M Kolesar

Cells (Basel, Switzerland), Vol.14(20), 1616

10/17/2025

DOI: 10.3390/cells14201616

PMCID: PMC12564448

PMID: 41148831

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Abstract

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer and immune-stimulating abilities of MVs. C-MVs had lower IC50s but equivalent DNA damage in OS cell lines when compared with free cisplatin. E-MVs and C-MVs were observed to accumulate in the tumor in OS tumor-bearing mice. C-MVs significantly reduced tumor burden and prolonged survival in a mouse model of OS. Animals dosed with free cisplatin experienced weight loss and renal and hepatic toxicity, while equivalent doses of C-MVs did not cause these effects. In addition, both E-MVs and C-MVs showed immunomodulation of the tumor microenvironment with a significant increase in the M1/M2 macrophages ratio (7-fold and 22-fold, respectively) and increased levels of TNF-α in serum (1.8-fold and 2.1-fold, respectively) compared to control mice. Collectively, these experiments support further development of C-MVs for the treatment of OS.

Animals

Antineoplastic Agents - pharmacology

Antineoplastic Agents - therapeutic use

Bone Neoplasms - drug therapy

Bone Neoplasms - pathology

Cell Line, Tumor

Cisplatin - pharmacology

Cisplatin - therapeutic use

Female

Humans

Macrophages - metabolism

Mice

Osteosarcoma - drug therapy

Osteosarcoma - pathology

RAW 264.7 Cells

Tumor Microenvironment - drug effects

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity in Osteosarcoma
Creators: Namrata Anand - University of Kentucky
Joseph Robert McCorkle - Markey Cancer Center
David S Schweer - Markey Cancer Center
Lan Li - University of Kentucky
Kristen S Hill - Markey Cancer Center
Melissa A Fath - University of Iowa
Derek B Allison - University of Kentucky
Christopher L Richards - University of Kentucky
Jill M Kolesar - University of Iowa
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.14(20), 1616
DOI: 10.3390/cells14201616
PMID: 41148831
PMCID: PMC12564448
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Publisher: MDPI
Grant note: 00000 / MIB Agents PON2 7282000002500 / Kentucky Cabinet For Health and Family Services
Language: English
Date published: 10/17/2025
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Obstetrics and Gynecology
Record Identifier: 9985019029402771

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