Reduction-responsive dextran-based Pt(IV) nano-prodrug showed a synergistic effect with doxorubicin for effective
Lin An1, Yuxi Jia1, Jinran Li2
1Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, China.
Abstract:
Melanoma, the deadliest skin cancer with high metastasis potential, has posed a great threat to human health. Accordingly, early efficient blocking of melanoma progression is vital in antitumor treatment. Herein, a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) was synthesized and used for doxorubicin (DOX) delivery to combat melanoma synergistically. First, PDPN was prepared by one-pot chemical coupling of carboxylated methoxy poly(ethylene glycol) (mPEG), dextran (Dex), and the crosslinking agent cisPt (IV)-COOH. PDPN had a spherical structure (Rh = 34 ± 11.3 nm). Then, DOX was encapsulated into the PDPN core to form DOX-loaded PDPN (PDPN-DOX). The obtained PDPN-DOX displayed reduction-responsive release of DOX and Pt, thus showing a synergistic anticancer effect in B16F10 cells (combination index, 0.46). Furthermore, in vivo experiments demonstrated that PDPN-DOX was effective for the synergistic treatment of subcutaneous melanoma. Collectively, the as-prepared PDPN could serve as a promising and versatile nano-prodrug carrier for the co-delivery of chemotherapeutics in tumor combination therapy.
Insights
A novel dextran-based platinum(IV) nano-prodrug (PDPN) effectively delivers doxorubicin (DOX) for synergistic melanoma treatment. This reduction-responsive system shows promise for combination cancer therapy.
Area of Science:
- Nanotechnology
- Oncology
- Materials Science
Background:
- Melanoma is a deadly skin cancer with high metastasis potential, necessitating early intervention.
- Efficiently blocking melanoma progression is crucial for effective antitumor treatment.
- Developing advanced drug delivery systems can enhance therapeutic outcomes.
Purpose of the Study:
- To synthesize a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) for synergistic melanoma treatment.
- To investigate the co-delivery of doxorubicin (DOX) using the developed nano-prodrug.
- To evaluate the efficacy of the nano-prodrug system in vitro and in vivo.
Main Methods:
- Synthesis of PDPN via one-pot coupling of mPEG, dextran, and cisPt(IV)-COOH.
- Encapsulation of DOX into PDPN to form PDPN-DOX.
- Characterization of PDPN-DOX particle size and morphology.
- Assessment of reduction-responsive drug release.
- Evaluation of synergistic anticancer effects in B16F10 cells and in vivo subcutaneous melanoma models.
Main Results:
- PDPN exhibited a spherical structure with a hydrodynamic radius of 34 ± 11.3 nm.
- PDPN-DOX demonstrated a reduction-responsive release of both DOX and platinum.
- A synergistic anticancer effect was observed in B16F10 cells with a combination index of 0.46.
- In vivo studies confirmed the effectiveness of PDPN-DOX in treating subcutaneous melanoma.
Conclusions:
- The synthesized PDPN serves as a promising nano-prodrug carrier.
- PDPN enables the co-delivery of chemotherapeutics for enhanced tumor treatment.
- This versatile platform holds potential for combination therapy in oncology.
