The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems

Abstract

Poly (adenosine diphosphate [ADP]-ribose) polymerases inhibitors (PARPi), the first clinically approved drug that exhibits synthetic lethality, are moving to the forefront of cancer treatments. Currently, the oral bioavailability of PARPi is quite low; thus, it is a major challenge to effectively and safely deliver PARPi during clinical cancer therapy. Nanotechnology has greatly advanced the development of drug delivery. Based on the basic characteristics and various forms of nanoparticles, drug delivery systems can prolong the time that drugs circulate, realize the controlled release of drugs, provide drugs with an active targeting ability, and spatiotemporally present combination treatment. Furthermore, nanosystems may not only enhance drug efficiency but also reduce adverse side effects. This review focuses on strategies involving nanoparticle-based delivery for PARPi, including single administration and codelivery with other agents. We believe that nanosystems have great potential in advancing PARPi efficacy for cancer therapy.

Keywords: PARP inhibitor; cancer therapy; drug delivery; nanosystem.

Figure 1

Different types of nanosystems for the delivery of PARP inhibitors in this review. (PARP: poly (adenosine diphosphate [ADP]–ribose) polymerases; MOF: metal-organic framework; SLN: solid lipid nanoparticle; NP: nanoparticle).

Figure 2

Schematic illustration of erythrocyte membrane-coated nanostructured lipid carriers (RBCNLCs) co-modified with C3 and SS31 peptide for brain neuronal mitochondria targeting to reduce the negative effects of mitochondrial PARP activation. (RBC: red blood cell; NLCs: nanostructured lipid carriers; NCAM: neural cell adhesion molecule; Ola: olaparib). Reprinted with permission from Ref. [50]. Copyright 2022 Elsevier, under the license number 5358651488895.

Figure 3

Schematic representation of DSA preparation and the antisenescence mechanism of DSAs in prostate cancer. (DSAs: Docetaxel−tannic acid self-assemblies). Reprinted with permission from Ref. [81]. Copyright 2019 American Chemical Society.

Figure 4

Schematic illustration of the design of the polymeric liposomal nanoparticle assembly with loaded therapeutic cargo and the treatment mechanism. (HA: hyaluronic acid). Reprinted from Ref. [84] under the terms of the Creative Commons CC BY license.

Figure 5

Schematic illustration of the design of MPM with loaded talazoparib and buparlisib, and the combined administration with radiation for enhanced DNA damage. (MPM: mixed poloxamer micelle; IR: irradiation). Reprinted with permission from Ref. [92]. Copyright 2019 American Chemical Society.