A Review of Silica-Based Nanoplatforms for Anticancer Cargo Delivery

Abstract

Stimuli-responsive silica nanoparticles have emerged as a promising platform for the targeted and controlled delivery of therapeutic agents in cancer therapy. These nanoparticles possess unique physicochemical properties that allow for the stimuli-triggered release of loaded cargos, such as drugs, enzymes, oligonucleotides, photosensitizers, and metals. The stimuli-responsive nature of these nanoparticles enables them to respond to specific internal and external signals within the tumor microenvironment, including pH, temperature, and redox potential, among others. This leads to the enhanced targeting of cancer cells and improved therapeutic efficacy while minimizing the off-target effects. This review highlights recent advances in the development and application of stimuli-responsive silica nanoparticles for the delivery of multiple active agents for cancer therapy. Overall, stimuli-responsive silica nanoparticles offer great potential for the development of more effective cancer therapies with improved selectivity and reduced side effects.

Keywords: cancer therapy; drug delivery; enzyme; mesoporous; metals; oligonucleotides; silica; stimuli responsive; tumor microenvironment.

Figure 4

Different examples from the literature of endogenous stimuli-responsive mesoporous silica nanoparticles for anticancer agent release. (A) pH: The antitumor drug DOX and photosensitizer ICG are adsorbed into the Mn-doped mesoporous nanorod pores and p(NIPAm-MA) is conjugated on the carrier surface to block the pores. The synthesized DOX-ICG@MMS/p(NIPAm-MA) displays a pH/light-responsive release. Reprinted with permission from Elsevier (reproduced from Chen, M. et al. [122]). (B) RedOx: Functionalization and cargo loading using mesoporous NPs with a disulfide-bridged silsesquioxane framework, and the further GSH-triggered degradation along with cargo release. Copyright permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim (reproduced from Du, X. et al. [130]). (C) Enzyme: Enzyme MMP-2-responsive-MSNs DDS for targeted tumor therapy in vitro and in vivo. The MSNs’ functionalization with the polypeptide consists of two components: the cell-penetrating peptide polyarginine and the MMP-2 cleavable substrate peptide (PVGLIG). PBA (Phenylboronic acid)–HAS (human serum albumin) is used as the end-capping agent for sealing the mesopores and immobilizing them onto the MSNs via the intermediate linker of polypeptides. Reprinted with permission from The Royal Society of Chemistry (reproduced with permission from Liu, L. [134]).

Figure 5

Different examples from the literature of external stimuli-responsive mesoporous silica nanoparticles for anticancer agent release. (A) Light: Design of functional CNT@MS nanocomposites to provide phototherapy combined with drug release mediated by NIR laser excitation. Copyright permission from Elsevier (reproduced from Li, B. [142]). (B) Ultrasounds: MSNs modified with sodium alginate with carboxyl–calcium (COO⁻-Ca²⁺) coordination bonds in the modified layer, blocking the mesopores. A rapid and significant cargo release is being produced by destroying the bonds under the coordinated stimulation of low-intensity ultrasound (20 kHz) or high-intensity focused ultrasound (HIFU, 1.1 MHz). Reprinted with permission from Frontiers (reproduced from Li, X. [148]).

Figure 7

Literature examples of different possible therapies exploiting silica-based nanomaterials as delivery systems. (A) Metal complexes therapy: Synthesis of Ru(II) polypyridine complex and folic acid-functionalized MSNs. Copyright permission from American Chemical Society (reproduced with permission from Karges, J. et al. [171]). (B) Chemodynamic therapy: Synthesis of FeOCl@H-DMOS-AA/PEG and schematic illustration of proposed CDT strategy. Reprinted with permission from American Chemical Society (reproduced with permission from Li, T. [208]).

Scheme 1

Flowchart of the main sections and topics covered in this review.

Figure 1

Scheme of different silica nanoparticles synthetic pathways with corresponding features.

Figure 2

Silica nanoparticles and their journey through body. Scheme describing silica nanomaterials biodistribution and clearance and particular features.

Figure 3

Scheme of silica nanoparticles responding to different stimuli to perform reactive release.

Figure 6

Literature examples of different possible therapies exploiting silica-based nanomaterials as delivery systems. (A) Oligonucleotide therapy: Biodegradable selenium-containing mesoporous silica nanocapsule capable of transporting and initiating RNAi by high-energy X-ray irradiation. Reprinted with permission from American Chemical Society (reproduced with permission from Tang, X. [153]). (B) Protein/enzyme therapy: Influence of MSN pores (dendritic mesoporous silica nanospheres (DMSNs) with funnel-shaped wide-open pores and fractal silica nanoparticles (FSNs)) on enzyme loading, release, and reusability. Copyright permission from Elsevier (reproduced from Kothalawala, S.G. et al. [158]). (C) PDT: Scheme of synthesis of MSN@SiNPs@TMPyP-FA for targeted two-photon-excited fluorescence imaging-guided PDT and chemotherapy. Reprinted with permission from Elsevier (reproduced from Li, S. et al. [173]).