Carrier-free nanodrugs with efficient drug delivery and release for cancer therapy: From intrinsic physicochemical properties to external modification

Abstract

The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability, simple preparation method, and offering "all-in-one" functional platform features. However, the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey, which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment. In this review, we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy, including optimizing the intrinsic physicochemical properties and external modification. Finally, the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented. We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.

Keywords: Carrier-free nanodrugs; Drug delivery and release; External modification; Intrinsic physicochemical properties; Therapeutic efficacy.

Graphical abstract

Fig. 1

Schematic illustration of the intrinsic physicochemical property optimization strategies and external modification strategies for drug delivery and release of carrier-free nanodrugs during the in vivo transportation from the blood to the targeted tumor sites.

Fig. 2

a) The size distribution of the different ratios of DOX to PhA. Reproduced with permission from Ref. [51]. Copyright 2018, Royal Society of Chemistry. b) The size distribution of the different ratios of Ce6 to DOX. Reproduced with permission from Ref. [52]. Copyright 2016, American Chemical Society. c) Size distribution and the Tyndall effect of different ratios of PTX to ICG. Reproduced with permission from Ref. [53]. Copyright 2019, Royal Society of Chemistry.

Fig. 3

a) The TEM images of CPT-ss-GEM nanowires and CPT-ss-GEM nanoparticles. Reproduced with permission from Ref. [66]. Copyright 2019, Elsevier. b) Schematic, TEM, and SEM images of IDM/PTX assemblies with different drug ratio. Reproduced with permission from Ref. [67]. Copyright 2019, American Chemical Society. c) The TEM images of CLA, PTX and CLA-PTX nanoparticles. Reproduced with permission from Ref. [68]. Copyright 2016, Springer Nature.

Fig. 4

The strategies to enhance carrier-free nanodrugs' stability. a) PEG-modified CPT nanocrystal through electrostatic interaction. Reproduced with permission from Ref. [86]. Copyright 2019, Royal Society of Chemistry. b) PDA fills the gap between DOX and Gn to form lollipop-like nanoparticles. Reproduced with permission from Ref. [92]. Copyright 2016, American Chemical Society. c) Cooperation between TA and Fe^III to form a coating that prevents Ostwald's maturation. Reproduced with permission from Ref. [94]. Copyright 2018, John Wiley and Sons.

Fig. 5

a) Schematic illustration of MHD−DI NPs for dual-targeting drug delivery and imaging-guided combinational chemo-PTT therapy. Reproduced with permission from Ref. [121]. Copyright 2019, American Chemical Society. b) CLSM images of cells co-incubated with DOX, UD NPs, and Ap/UD NPs for 2 h. Reproduced with permission from Ref. [129]. Copyright 2017, Royal Society of Chemistry. c) In vivo fluorescence imaging of PTN at different times after intravenous injection. Reproduced with permission from Ref. [131]. Copyright 2018, John Wiley and Sons. d) Schematic illustration of the preparation of carrier-free nanosystems based on packing the DOX and ICG coassembly nanoparticles with CCCMs. Reproduced with permission from Ref. [135]. Copyright 2018, Elsevier.

Fig. 6

a) The formation of Ir-Bd and its mechanism in vivo. b) Drug release curve of Ir-Bd. Reproduced with permission from Ref. [171]. Copyright 2015, Royal Society of Chemistry. c) The preparation process and “bomb-like” drug release of DNPs/N@PDA and enhanced chemo-/photothermal therapy triggered by NIR irradiation. Reproduced with permission from Ref. [187]. Copyright 2018, John Wiley and Sons.