Novel Tumor-Targeting Nanoparticles for Cancer Treatment-A Review

Abstract

Being one of the leading causes of death and disability worldwide, cancer represents an ongoing interdisciplinary challenge for the scientific community. As currently used treatments may face limitations in terms of both efficiency and adverse effects, continuous research has been directed towards overcoming existing challenges and finding safer specific alternatives. In particular, increasing interest has been gathered around integrating nanotechnology in cancer management and subsequentially developing various tumor-targeting nanoparticles for cancer applications. In this respect, the present paper briefly describes the most used cancer treatments in clinical practice to set a reference framework for recent research findings, further focusing on the novel developments in the field. More specifically, this review elaborates on the top recent studies concerning various nanomaterials (i.e., carbon-based, metal-based, liposomes, cubosomes, lipid-based, polymer-based, micelles, virus-based, exosomes, and cell membrane-coated nanomaterials) that show promising potential in different cancer applications.

Keywords: cancer management; cancer treatment; combined cancer therapies; controlled drug delivery; nanomedicines; novel nanocarriers; theranostics; tumor-targeting nanoparticles.

Figure 1

The updated landscape of tumor microenvironment (TME). Reprinted from an open-access source [46]. Abbreviations: CAF—cancer-associated fibroblasts; DC—dendritic cells; ECM—extracellular matrix; MDSC—myeloid-derived suppressor cells; PNI—perineural invasion; ROS—reactive oxygen species TAM—tumor-associated macrophages; TAN—tumor-associated neutrophils.

Figure 2

Schematic representation of the role of TME and intracellular signals in tumor targeting and controlled drug release. Reprinted from an open-access source [49]. Abbreviations: ATP—adenosine triphosphate; ROS—reactive oxygen species.

Figure 3

Schematic representation of various nanomaterials researched for tumor-targeting applications.

Figure 4

The role of Carbon-based nanomaterials in TME-targeted cancer therapy. Adapted with permission from [44]. Copyright 2018, John Wiley and Sons. Abbreviations: ECM—extracellular matrix; ROS—reactive oxygen species.

Figure 5

Schematic representation of the delivery system designed by Chen et al. (A) Nanosystem fabrication. (B) Mechanisms of action. Reprinted from an open-access source [52]. Abbreviations: CS—chitosan; DEPC—diethylpyrocarbonate; EDC—N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide; GCE—GO-CS/anti-EpCAM; GO—graphene oxide; MES—2-(N-morpholino) ethanesulfonic acid; NHS—N-hydroxysuccinimide.

Figure 6

Application of external and internal stimuli-triggered metallic nanotherapeutics for cancer treatment. Reprinted from an open-access source [65]. Abbreviations: AMF—alternative magnetic field; GSH—glutathione; GSSG- glutathione disulfide; ROS—reactive oxygen species; US—ultrasound.

Figure 7

Schematic representation of a multifunctional liposome-based nanoparticle.

Figure 8

Schematic representation of the enhanced tumor retention of nanovehicles designed by Lu et al. by virtue of acid-triggered surface charge neutralization and agglomeration. Reprinted with permission from [103]. Copyright 2020, Elsevier.

Figure 9

(a) Design of bone-targeted, protein-functionalized, dendrimer-based nanomedicine for treating malignant bone tumors. (b) Schematic representation of the mode of action of the developed nanosystem. Reprinted from an open-access source [113]. Abbreviations: GP—G5-phenylboronic acid; GPS—GP-saporin complex; GPSP—GPS-PASP ternary complex; i.v.—intravenously; PASP—poly-(α, β)-DL-aspartic acid.

Figure 10

Schematic representation of polymeric micelles. Reprinted from an open-access source [118]. Abbreviation: CMC—critical micellar concentration.

Figure 11

Schematic representation of the (a) synthesis, (b) delivery process, and (c) mode of action of VLPs designed by Liu et al. Reprinted with permission from [133]. Copyright 2020, Elsevier. Abbreviations: Axi—axitinib; GSH—glutathione; MSN—mesoporous silicon nanoparticle; RMSN—ribonucleoprotein-conjugated MSN; VLN—virus-like nanoparticle.

Figure 12

The influence of exosomes on tumor progression. Promoting tumors: (A) including the regulation of the secretion of mediators of angiogenesis; (B) promoting the immune escape by regulating macrophage polarization and inhibiting T cell activation; (C) stimulates tumor cell proliferation by affecting signaling pathways; (D) the tumor microenvironment mediates cancer-associated fibroblast (CAF) formation by educating MSCs-Exo; (E): MSCs-Exo increase drug resistance. Inhibiting tumors: (a) inhibition of angiogenesis; (b) inhibition of tumor proliferation through miRNA-mediated signaling pathways; (c) increase the number and sensitivity of T cells and NK cells; (d) improving drug sensitivity. Reprinted from an open-access source [145].

Figure 13

Schematic representation of doxorubicin loading into neutrophil-exosomes, BBB crossing of the nanosystem, and inflammatory stimuli-responsive drug delivery. Reprinted with permission from [149]. Copyright 2021, Elsevier. Abbreviations: BBB—blood-brain barrier; DOX—doxorubicin.

Figure 14

Rh2@HMnO₂-AM synthesis procedure and the mechanism of MRI-guided immuno-chemodynamic synergistic osteosarcoma therapy. Reprinted from an open-access source [162].

Figure 15

Schematic representation of theranostics.