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Enhancing PARP inhibitor efficacy using reduction-responsive nanoparticles encapsulating NADP.

Hao Chen¹, Fan Tan¹, Yukui Zhang^1,2

¹Key Laboratory of Molecular Medicine and Biological Diagnosis and Treatment (Ministry of Industry and Information Technology), School of Life Science, Beijing Institute of Technology, Beijing 100081, China. xiebingteng@bit.edu.cn.

Journal of Materials Chemistry. B

|December 3, 2024

Summary

This summary is machine-generated.

This study developed nanoparticles delivering NADP+ to sensitize tumors to PARP inhibitors like olaparib. This combination therapy effectively suppresses tumor cell growth by enhancing DNA repair inhibition.

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Area of Science:

Biochemistry
Nanotechnology
Oncology

Background:

Poly(ADP-ribose) polymerase inhibitors (PARPi) are effective cancer treatments, but resistance limits their use.
NADP+ inhibits ADP-ribosylation and can sensitize cancer cells to PARPi, but its poor cell membrane permeability is a challenge.

Purpose of the Study:

To develop a nanoparticle delivery system for NADP+ to overcome its permeability issues.
To investigate the synergistic effect of NADP+-loaded nanoparticles and olaparib on tumor cell growth.

Main Methods:

Designed reduction-responsive nanoparticles (NPs) with disulfide bonds for intracellular NADP+ release.
Encapsulated NADP+ and olaparib within these NPs.
Evaluated NP uptake, intracellular NADP+ levels, and effects on DNA damage repair and tumor cell proliferation.

Main Results:

NPs successfully delivered NADP+ into tumor cells, increasing intracellular concentrations.
Elevated NADP+ inhibited DNA damage-induced PARylation and impaired DNA repair.
Combined NADP+ and olaparib treatment synergistically suppressed tumor cell growth.

Conclusions:

Reduction-responsive nanoparticles offer a viable strategy for delivering NADP+ to cancer cells.
This NADP+-based nanoparticle system combined with olaparib shows significant potential for cancer therapy.