Nanocarrier cancer therapeutics with functional stimuli-responsive mechanisms

Abstract

Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future.

Keywords: Cancer therapy; Functional nanocarriers; Smart drug delivery; Stimulus-responsive drug release.

Fig. 1

Intracellular applications of nanocarriers designed using different materials. The type and functionality of the nanocarrier are controlled by its shape, size, and targeting ligands, leading to high maneuverability and target-specific drug delivery

Fig. 2

Examples of inorganic nanocarriers. Mesoporous nanoparticles are silica nanoparticles with overall diameter of < 1 μm and pores diameter from 2 to 50 nm. Quantum dots are colloidal fluorescent semiconductor nanocrystals (2–10 nm). Silver and gold nanoparticles (1–100 nm) have high surface area, tunable optical, and are non-toxic. Carbon nanotubes consist of coaxial graphite sheets (< 100 nm) rolled up cylindrical. Graphene oxide is single atomic layer of carbon, consist of thickness 1 nm. Figure has been created using Biorender

Fig. 3

Schematic representation of the different types of liposomal drug delivery systems. A Conventional liposomes consist of a lipid bilayer surrounding aqueous compartments, composed of phospholipids and cholesterol unmodified B PEGylated liposomes have a hydrophilic polymer coating (PEG) on the surface of the liposome that modifies in vivo characteristics and behavior via steric stabilization. C Ligand-targeted liposomes can affect specific targets via ligands attached to the surface or terminal end of the attached PEG chains. D Theranostic liposomes are a single system consisting of a nanoparticle, a targeting element, an imaging component, and a therapeutic component. Figure has been created using Biorender

Fig. 4

Potential cell surface proteins and their complementary receptors for use in targeted-drug delivery applications. t-SNARE/v-SNARE target snap receptor/vesicle snap receptor; PS phosphatidylserine; C1q complement component 1q; SCARF-1 scavenger receptor class-F, member-1; Gp1b glycoprotein-Ib; TSP-2 thrombospondin-2; SIRPα signal regulatory protein α; CD cluster of differentiation; ICAM intercellular adhesion molecule; LFA-1 lymphocyte function-associated antigen-1; MAC-1 macrophage adhesion ligand-1; VLA very late antigen; PAMP pathogen associated molecular pattern; DAMP damage-associated molecular pattern; PD-1/PD-2 programmed cell death protein-1/programmed cell death protein-2; PD-L1/PD-L2 programmed death-ligand-1/programmed death-ligand-2; CTLA-4 cytotoxic t-lymphocyte-associated protein-4; TRAIL tumor necrosis factor-related apoptosis-inducing ligand; TNF tumor necrosis factor; B7-H6 B7 homolog 6; MIC MHC class I polypeptide-related sequence; H60 histocompatibility protein-60; NKp natural cytotoxicity triggering receptor; NKG natural killer cell granule protein; KIR killer-cell immunoglobulin-like receptor; LIR leukocyte immunoglobulin-like receptor; HMGβ1 high-mobility group protein β1; RAGE receptor for advanced glycation end products. Figure has been created using Biorender

Fig. 5

Schematic representation of polymeric micelles. Self-assembly of di-block copolymers into a polymeric micelle takes place above the critical aggregation concentration. The hydrophobic drug is encapsulated into the hydrophobic core. Figure has been created using Biorender

Fig. 6

Schematic illustration of drug release. In response to either internal (pH, redox, enzyme) or external (thermo, magnetic field, light) stimuli. Figure has been created using Biorender

Fig. 7

Mechanisms of targeting NCs to tumors. A Passive targeting by nanomedicines is due to the enhanced permeability and retention (EPR) effect, which involves their extravasation from leaky tumor vasculature and poor lymphatic drainage. B Active targeting is achieved by functionalizing nanomedicines with targeting ligands that recognize tumor cell receptors, which increases cell specificity and uptake. Figure has been created using Biorender