Recent progress in nanomedicine for enhanced cancer chemotherapy

Abstract

As one of the most important cancer treatment strategies, conventional chemotherapy has substantial side effects and leads easily to cancer treatment failure. Therefore, exploring and developing more efficient methods to enhance cancer chemotherapy is an urgently important problem that must be solved. With the development of nanotechnology, nanomedicine has showed a good application prospect in improving cancer chemotherapy. In this review, we aim to present a discussion on the significant research progress in nanomedicine for enhanced cancer chemotherapy. First, increased enrichment of drugs in tumor tissues relying on different targeting ligands and promoting tissue penetration are summarized. Second, specific subcellular organelle-targeted chemotherapy is discussed. Next, different combinational strategies to reverse multidrug resistance (MDR) and improve the effective intracellular concentration of therapeutics are discussed. Furthermore, the advantages of combination therapy for cancer treatment are emphasized. Finally, we discuss the major problems facing therapeutic nanomedicine for cancer chemotherapy, and propose possible future directions in this field.

Keywords: cancer therapy; chemotherapy; combination therapy; nanocarriers; nanomedicine.

Figure 1

Schematic illustration of nanocarrier-based drug delivery systems (NDDS) for improving cancer chemotherapy based on different strategies. (A) Targeted drug delivery . Copyright 2016, ACS Publications, (B) Promoting tissue penetration . Copyright 2016, ACS Publications, (C) Mitochondria-targeted chemotherapy . Copyright 2018, Elsevier, (D) Nucleus-targeted chemotherapy . Copyright 2015, Wiley-VCH, (E) Golgi-targeted chemotherapy . Copyright 2019, ACS Publications, (F) Inhibition of P-gp . Copyright 2017, Wiley-VCH, (G) π-π stacked dual anticancer drug . Copyright 2016, Wiley-VCH, (H) Combination with PDT . Copyright 2020, Wiley-VCH, (I) Combination with PTT . Copyright 2020, Wiley-VCH, (J) Combination with CDT . Copyright 2020, ACS Publications, (K) Combination with radiotherapy . Copyright 2017, Wiley-VCH, (L) Combination with gas therapy . Copyright 2018, ACS Publications, (M) Combination with immunotherapy . Copyright 2021, Elsevier, (N) Multiple combination therapy . Copyright 2019, Wiley-VCH.

Figure 2

(A) Illustration of the self-assembly and intracellular trafficking pathway of redox-sensitive HA-ss-DOCA micelles . Copyright 2012, Elsevier. (B) PBA ligand-mediated endocytosis and Intracellular drug release triggered by GSH . Copyright 2016, ACS Publications.

Figure 3

(A) Schematic illustration of the self-assembly of PEG-b-PAEMA-PAMAM/Pt into the pH-sensitive cluster nanobombs (SCNs/Pt) at neutral pH and the disintegration of SCNs/Pt into small particles at tumor acidic pH . Copyright 2016, ACS Publications. (B) Fabrication and response of size-changeable collagenase-modified nanoscavenger (CS/Col-TCPPB NPs) . Copyright 2020, Wiley-VCH.

Figure 4

(A) The schematic illustration of drug delivery system with mitochondrial alkaline pH-responsive release . Copyright 2018, Elsevier. (B) The schematic illustration of Tat-mediated enhanced endocytosis into tumor cells and nuclear targeting . Copyright 2018, Wiley-VCH.

Figure 5

(A) Schematic illustration of the fabrication of phototriggered NO nanogenerators (PTNGs) . Copyright 2017, Wiley-VCH. (B) Schematic illustration of combination of DOX and HCPT using a multifunctional micelle to combat MDR and lung metastases . Copyright 2016, Wiley-VCH.

Figure 6

(A) Formation and mechanism of TPZ/AI-NV for dissociation of vehicles and simultaneous activation of bioreductive prodrug . Copyright 2017, Wiley-VCH. (B) Schematic of F@PDA-TPP/SS/DOX for synergism of PTT and chemotherapy . Copyright 2018, Wiley-VCH.

Figure 7

(A) Schematic illustration of PtH@FeP-mediated antitumor synergistic therapy by combining CDDP-induced apoptosis and CDT-based ferroptosis . Copyright 2020, ACS Publications. (B) Scheme illustrating the redox/pH responsive behaviors of BM@NCP(DSP)-PEG composite nanoparticles in the tumor microenvironment for cancer chemoradiotherapy . Copyright 2017, Wiley-VCH.

Figure 8

(A) Schematic of AlbSNO and Ptx@AlbSNO preparation. (B) Tumor-specific release of NO from Ptx@AlbSNO possesses the dual functions of simultaneously preventing tumor metastasis and reversing tumor immunosuppression by blocking platelets . Copyright 2020, ACS Publications.

Figure 9

(A) Schematic illustration of the carrier-free nanoassembly PEG@D:siRNA for combinationally inducing ICD and reversing immunosuppression . Copyright 2020, Elsevier. (B) Schematic illustration of LMWH/PPD/CpG to inhibit melanoma primary tumor and pulmonary metastasis . Copyright 2019, Ivyspring International Publisher. (C) Schematic illustration of the enhanced cancer chemo-immunotherapy resulting from intratumorally and intravenously injected nanomedicines . Copyright 2019, Elsevier.

Figure 10

(A) Schematic illustration of BP-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer . Copyright 2017, Wiley-VCH. (B) Rational design and synthesis of FA-CD@PP-CpG nanocomposites (top), its application in cancer treatment (left), and illustration of FA-CD@PP-CpG for docetaxel-enhanced immunotherapy (right) . Copyright 2019, Wiley-VCH.