Moving Beyond the Pillars of Cancer Treatment: Perspectives From Nanotechnology

Abstract

Nanotechnology has made a significant impact on basic and clinical cancer research over the past two decades. Owing to multidisciplinary advances, cancer nanotechnology aims to address the problems in current cancer treatment paradigms, with the ultimate goal to improve treatment efficacy, increase patient survival, and decrease toxic side-effects. The potential for use of nanomedicine in cancer targeting and therapy has grown, and is now used to advance the four traditional pillars of cancer treatment: surgery, chemotherapy, radiation therapy and the newest pillar, immunotherapy. In this review we provide an overview of notable advances of nanomedicine in improving drug delivery, radiation therapy and immunotherapy. Potential barriers in the translation of nanomedicine from bench to bedside as well as strategies to overcome these barriers are also discussed. Promising preclinical findings highlight the translational and clinical potential of integrating nanotechnology approaches into cancer care.

Keywords: drug delivery; immunotherapy; nanomedcine; radiation therapy; theranosctics.

Figure 1

(A) pH-dependent nanoparticle decomposition of hollow MnO₂-PEG nanoparticles dispersed in solutions of different pH (7.4, 6.5, and 5.5) determined by the absorbance of MnO₂. (B) Percentages of released Ce6 and DOX from H-MnO₂-PEG/C&D over time in the presence of 10% fetal bovine serum (FBS) at different pH values. (C) In vivo axial T1-MR images of a 4T1- tumor bearing mouse taken before and 24 h post i.v. injection of H-MnO₂-PEG/C&D. (D) Tumor growth curves in different groups after various treatments as indicated. Chemo-PDT treatment after injection of pH-responsive H-MnO₂-PEF/C&D nanoparticles depicted most significant reduction in tumor volumes. With permission from Yang et al. (2017). p values were calculated by Tukey's post-test (***p < 0.001, **p < 0.01, and *p < 0.05).

Figure 2

(A) Schematic illustration of Enzyme-Responsive Polyprodrug Nanoplatforms, composed of ICG and cisplatin polyprodrug amphiphiles tethered with repeating cathepsin-B degradable GFLG peptides, PEG-b-P(Pt-co-GFLG)-b-PEG. (B) In vitro Pt release under different treatment conditions: (i) pH 7.4 without papain (physiological condition), (ii) pH 5.5 with papain, simulating the acidic and enzymatic condition of lysosomes, (iii) pH 5.5 with papain in the presence of a papain inhibitor, and (iv) pH 5.5 with papain followed by GSH treatment at pH 7.4, mimicking the lysosomal escape into the reductive cytosolic environment. (C) Fluorescence images of cathepsin B positive A549 cells and cathepsin B negative L-O2 cells upon incubation with ICG/Poly(Pt) after irradiation with 808 nm, 1 W/cm², 5 min. Viable cells were stained with green Calcein-AM, while dead and late apoptotic cells were stained with red PI. Scale bar: 40 um. (D) Survival curves of resistant A549/DDP cancerous mice after cascade photo-chemotherapy. Figure adapted with permission from Wang W. et al. (2018).

Figure 3

(A) Schematic illustration for the synthesis and structure of W-GA-PEG CPNs. (B) In vivo PET images of 4T1-tumor-bearing mice after i.v. injection of 64Cu-W-GA-PEG CPNs at different time points. The tumors are indicated with yellow arrows. (C) The W levels in urine and feces of healthy mice after i.v. administration of W-GA-PEG CPNs (dose = 40 mg/kg) collected at different intervals. (D) Tumor growth curves and (E) survival curves of animals treated with W-GA-PEG CPN or radiotherapy or both (five mice per group; irradiation dose of X-ray (RT): 6 Gy; injection dose of W-GA-PEG CPNs: 20 mg/kg). Figures adapted from Shen et al. (2017).

Figure 4

(A) Schematic illustration of PLGA-ICG-R837-based PTT and anti-CTLA-4 combination therapy to inhibit tumor growth at distant sites. (B) Morbidity-free survival of different groups of mice with metastatic 4T1 tumors after various treatments to eradicate their primary tumors: (1) Surgery, (2) Surgery+antiCTLA4, (3) Surgery+ PLGA-ICG-R837, (4) PLGA-ICG-R837+laser, (5) Surgery+ PLGA-ICG-R837+antiCTLA4, and (6) PLGA-ICG-R837+ laser + antiCTLA4. (C) CD8+ CTL: Treg ratios and CD4+ effector T cells: Treg ratios in the secondary tumors upon various treatments. Both ratios were significantly enhanced after combination treatment with PLGA-ICG-R837-based PTT and anti-CTLA4 therapy. Figure adapted with permission from Chen et al. (2016).

Figure 5

Schematic illustrating the potential of nanotechnology in advancing the pillars of modern cancer treatment toward effective, affordable and accessible personalized medicine to improve healthcare outcomes.