Aptamer-Based Smart Targeting and Spatial Trigger-Response Drug-Delivery Systems for Anticancer Therapy

Abstract

In recent years, the field of drug delivery has witnessed remarkable progress, driven by the quest for more effective and precise therapeutic interventions. Among the myriad strategies employed, the integration of aptamers as targeting moieties and stimuli-responsive systems has emerged as a promising avenue, particularly in the context of anticancer therapy. This review explores cutting-edge advancements in targeted drug-delivery systems, focusing on the integration of aptamers and stimuli-responsive platforms for enhanced spatial anticancer therapy. In the aptamer-based drug-delivery systems, we delve into the versatile applications of aptamers, examining their conjugation with gold, silica, and carbon materials. The synergistic interplay between aptamers and these materials is discussed, emphasizing their potential in achieving precise and targeted drug delivery. Additionally, we explore stimuli-responsive drug-delivery systems with an emphasis on spatial anticancer therapy. Tumor microenvironment-responsive nanoparticles are elucidated, and their capacity to exploit the dynamic conditions within cancerous tissues for controlled drug release is detailed. External stimuli-responsive strategies, including ultrasound-mediated, photo-responsive, and magnetic-guided drug-delivery systems, are examined for their role in achieving synergistic anticancer effects. This review integrates diverse approaches in the quest for precision medicine, showcasing the potential of aptamers and stimuli-responsive systems to revolutionize drug-delivery strategies for enhanced anticancer therapy.

Keywords: aptamer; stimuli-responsive drug delivery; targeted drug delivery.

Figure 1

A variety of aptamer conjugates for targeted drug-delivery system.

Figure 2

Carbon nanomaterials (CNMs) for theranostics.

Figure 3

Schematic illustration of the PEG−detachable nanoparticles in the tumor microenvironment for enhanced immunotherapy (Reprinted with permission from ref. [86] and from Elseiver. Copyright 2022, Elsevier). (a) Synthetic scheme of hypoxia responsive poly (I:C) delivery nanoparticle. (b) Mechanism of immunotherapy in response to TME-sensitive PEG-detaching nanoparticles.

Figure 4

Schematic illustration of the charge conversion system in the TME for anticancer therapy (Reprinted from ref. [103], with permission from Elseiver. Copyright 2022, Elsevier).

Figure 5

Schematic illustration of crosslinked nanoparticle system in TME for enhanced antitumor activity (Reprinted with permission from ref. [106] under the terms of the Creative Commons CC BY license. Copyright 2022, Springer Nature). (a) Schematic illustration of the bioorthogonal reaction under TME. (b) Mechanism of prolonged drug release when D-NPs and C-NPs were co-administrated in the TME.

Figure 6

ROS−responsive drug delivery system for anticancer immunotherapy (Reprinted with permission from ref. [112] under the terms of the Creative Commons CC BY license. Copyright 2023, John Wiley and Sons).

Figure 7

Preparation of the core–shell nanodroplet for spatiotemporal anticancer drug delivery at tumor tissue (Reprinted from ref [126], with permission from Elsevier. Copyright 2021, Elsevier).

Figure 8

US-mediated ROS generation for synergistic anticancer therapy combined with sonodynamic ROS-mediated therapy with accelerated release of immunotherapeutic agents (Reprinted with permission from ref. [130] under the terms of the Creative Commons CC BY license. Copyright 2022, Springer Nature). (a) Schematic illustration of the release of NLG919 and anti−PD−L1 antibody from sonosensitizer−loaded US−responsive nanoparticle. (b) Mechanism of US-mediated anticancer therapy under US irradiation with US−responsive nanoparticles.

Figure 9

Thermal-sensitive drug-delivery system for synergistic anticancer therapy (Reprinted from ref. [147]. Copyright 2019, Ivyspring International Publisher).

Figure 10

Schematic illustration of HIFU-mediated therapeutic agent delivery system for enhanced anticancer therapy. HIFU generated NO at tumor tissue, which accelerated DOX accumulation to increase anticancer effect (Reprinted from ref. [155], with permission from Elseiver. Copyright 2019, Elsevier).

Figure 11

(a) Schematic illustration of the nanoparticle with pH−responsive (a1,a2) and NIR−responsive (a2,a3) drug release characteristics. (b) Schematic illustration of the synergetic chemo−photothermal therapy for tumor cell with the nanoparticles (Reprinted with permission from ref. [186]. Copyright 2021, American Chemical Society).

Figure 12

Schematic illustration of photothermal-induced DNA dynamics for anticancer therapy. (a) Scheme of DNA-incorporated gold nanoparticle with Que loading. (b) Mechanistic illustration of anticancer effect of nanoparticle upon light irradiation (Reprinted with permission from ref. [203] under the terms of the Creative Commons CC BY license. Copyright 2023, Springer Nature).

Figure 13

Schematic illustration of ROS-responsive polymersomes for ROS-mediated drug delivery with PDT (Reprinted from ref. [210], with permission from Elsevier. Copyright 2020, Elsevier).

Figure 14

Schematic illustration depicting the incorporation of the GA-prodrug and UA-RNA in UCNPs for NIR-activatable synergistic anticancer therapy (Reprinted from ref. [218]. Copyright 2023, Royal Society of Chemistry).

Figure 15

Schematic illustration of microbubbles incorporating MNPs for a dual stimuli-responsive drug-delivery system, responsive to both a magnetic field and ultrasound (Reprinted with permission from ref. [226]. Copyright 2020, American Chemical Society).

Figure 16

An overall strategy involves the utilization of MH-responsive nano-assembled MNPs for synergistic anticancer therapy, combining magnetic-guided therapy with immunotherapy (Reprinted from ref. [228], with permission from Elsevier. Copyright 2023, Elsevier).