Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment

Abstract

Conventional chemotherapy for cancer treatment is usually compromised by shortcomings such as insufficient therapeutic outcome and undesired side effects. The past decade has witnessed the rapid development of combination therapy by integrating chemotherapy with hyperthermia for enhanced therapeutic efficacy. Near-infrared (NIR) light-mediated photothermal therapy, which has advantages such as great capacity of heat ablation and minimally invasive manner, has emerged as a powerful approach for cancer treatment. A variety of nanomaterials absorbing NIR light to generate heat have been developed to simultaneously act as carriers for chemotherapeutic drugs, contributing as heat trigger for drug release and/or inducing hyperthermia for synergistic effects. This review aims to summarize the recent development of advanced nanomaterials in chemo-photothermal combination therapy, including metal-, carbon-based nanomaterials and particularly organic nanomaterials. The potential challenges and perspectives for the future development of nanomaterials-based chemo-photothermal therapy were also discussed.

Keywords: NIR responsive; cancer; chemo-photothermal therapy; nanomaterials; synergistic effect.

Figure 1

AuNPs-based nanoplatforms for NIR light-responsive chemo-photothermal therapy. Hollow gold nanospheres, reproduced with permission from You et al. (2012); Gold nanorods, reproduced with permission from Xiao et al. (2012); Gold nanocages, reproduced with permission from Yavuz et al. (2009); Gold nanstars, reproduced with permission from Li M. et al. (2016); Gold nanoshells, reproduced with permission from Park et al. (2009); Gold Janus nanoparticles, reproduced with permission from Zhang L. et al. (2016).

Figure 2

Different copper chalcogenides nanocrystals mediated chemo-photothermal therapy. (A) Schematic illustration and TEM image of PEG-Fol-Cu₂S nanoparticles, and photoexcitation mediated drug release. Reproduced with permission from Poulose et al. (2015). (B) Schematic illustration and TEM image of Cu_2−xSe@mSiO₂-PEG nanoparticles, and synergistic effects on cell viability and tumor volume. Reproduced with permission from Liu et al. (2014). (C) TEM image of PEG-Cu_2−xTe nanocubes and effects of chemo-photothermal treatment on cell viability and cellular apoptosis. Reproduced with permission from Poulose et al. (2016).

Figure 3

2D TMDCs for combined chemo-photothermal therapy. (A) Schematic illustration of DOX loaded ATPMC for NIR-laser irradiation-induced chemotherapy. TEM image of MoS₂/Cu_1.8S nanosheets and tumor volume change with different treatments (*P < 0.01 compared with control group; ^#P < 0.01 compared with ATPMCD group). Reproduced with permission from Meng et al. (2017). (B) FESEM image of MoS₂@BSA nanoparticles and combined therapeutic efficacy of MoS₂@BSA-DOX in 4T1 cells (**P < 0.01 compared with MoS₂@BSA-DOX + NIR group). Reproduced with permission from Chen L. et al. (2016). (C) TEM image of MoS₂@SiO₂-NH₂ nanoplates and NIR-induced cytotoxicity of DOX-MoS₂@SiO₂-PEG against HepG2 cells (**P < 0.01). Reproduced with permission from Lee et al. (2016). (D) TEM image of MoSe₂@PDA nanocomposites and tumor growth curves of different treatments. Reproduced with permission from Wang C. et al. (2016). (E) TEM image of WS₂-IO@MS-PEG and growth of 4T1 tumors in different groups of mice after various treatments (***P < 0.001, *P < 0.05). Reproduced with permission from Yang G. B. et al. (2015).

Figure 4

C-dots- and MCNs-based chemo-photothermal therapy. (A) Schematic illustration of CND-P and cell viability with different treatments. Reproduced with permission from Ardekani et al. (2017). (B) Schematic illustration of GdN@CQDs/GP and relative tumor volume of tumor-bearing mice after various treatments. Reproduced with permission from Zhang et al. (2017a). (C) Schematic illustration of MCNs, and cytotoxicity assays of MDA-MB-231 cells under different treatments. Reproduced with permission from Zhou et al. (2015). (D) Schematic illustration of FPC-NCs and in vitro cytotoxicity after various treatments. Reproduced with permission from Wang H. et al. (2015).

Figure 5

Polymeric prodrug micelles as nano-carriers for NIR dye. (A) Schematic representation of IR-780 loaded polymeric prodrug micelle for chemo-photothermal therapy to overcome drug resistance. (B) Temperature increments of IR-780 loaded micelles upon 808 nm NIR laser irradiation. (C) Subcellular localization of free DOX, free IR-780, IPM, and IPM plus NIR laser irradiation after coincubation with MCF-7/ADR cells. (D) Quantitative evaluation of cell viability in MCF-7/ADR cells after different treatments (*P < 0.05, **P < 0.01). (E) MCF-7/ADR tumor growth curves subjected to different treatments. Reproduced with permission from Li Z. H. et al. (2016).

Figure 6

Multifunctional nanoparticles for light-controlled pulsatile drug release in cancer chemo-photothermal therapy. (A) Schematic illustration of the synthesis of CPT@DOX-UCST/PPy nanoparticles. (B) Thermal images recorded for different contents of CPT@DOX-UCST/PPy upon irradiation with 808 nm laser at different power density. (C) In vitro CPT and DOX dual drug release profile recorded for CPT@DOX-UCST/PPy with periodic 808 nm laser illumination at 2 W/cm². (D) Photographs of tumor tissue of mice upon different treatments. Reproduced with permission from Yang et al. (2018).

Figure 7

Carrier-free “Nanobomb” for on demand drug release and enhanced chemo-photothermal therapy. (A) Schematic illustration of the preparation of DNPs/N@PDA. (B) Schematic illustration of the stable blood circulation of DNPs/N@PDA and on demand “bomb-like” drug release and enhanced chemo-photothermal therapy triggered by NIR irradiation. (C) TEM images of DNPs/N@PDA before and after NIR laser irradiation (808 nm, 5 W/cm²) for 5 min. (D) Temperature increase profiles of PBS, DNPs, DNPs@PDA, and DNPs/N@PDA with NIR laser irradiation of 808 nm (5 W/cm², 8 min). (E) Cumulative release profiles of DOX from DNPs, DNPs@PDA, and DNPs/N@PDA in PBS with different pHs without or with NIR irradiation (808 nm, 5 W/cm², 5 min). (F) In vitro cytotoxicity of DNPs, DNPs@PDA, and DNPs/N@PDA at pH 5.0 with NIR laser irradiation (808 nm) of 5 W/cm² for 1 min at different DOX concentrations on HeLa cells after 48 h incubation (**p < vs. DNPs/N@PDA group with NIR irradiation). (G) Representative photos of excised tumors 21 d after treatments. Reproduced with permission from Li M. H. et al. (2018).