Functional Nucleic-Acid-Decorated Spherical Nanoparticles: Preparation Strategies and Current Applications in Cancer Therapy

Abstract

Functional nucleic acids (FNAs) have drawn widespread attention in the construction of functional nanomaterials for biomedical applications due to their inherent biological functions and sequence programmability, as well as high thermal stability and easy chemical modification. FNA-decorated spherical nanoparticles (FSNPs) are composed of a metal/metal-free spherical core and a radially oriented FNA shell. Attracted by their unique capabilities, such as resistance to nuclease degradation and capability of crossing the blood-brain barrier, FSNPs as smart nanomaterials for cancer therapy are reviewed. The preparation strategies of FSNPs are first summarized, and the applications of responsive linkers in stimuli-responsive drug release are introduced. The FSNPs are categorized into aptamer-, i-motif-, DNAzyme-, antisense oligonucleotide-, and CpG oligodeoxynucleotide-decorated SNPs. Their applications in cancer therapy include tumor-targeting drug delivery and controllable releasing of drugs, overcoming physiological or pathological obstacles such as blood-brain barrier and interstitial transport barriers, as well as a reversal of resistance to chemotherapy and antitumor immune response activation. The remaining challenges and future directions of FSNPs are also discussed and proposed.

Keywords: cancer therapy; controlled drug release; functional nucleic acids; nucleic acids linking strategies; spherical nanoparticles; targeted drug delivery.

Figure 1

a) The AS1411‐prodrug conjugate self‐assembled micelles encapsulating hemin for the depletion of cancerous antioxidant defense and enhanced CDT. Reproduced with permission.^{[ 89 ]} Copyright 2019, American Chemical Society. b) Schematic illustration for the fabrication process of AFT‐PLN@Map. Reproduced under the terms of the CC‐BY 4.0 license.^{[ 93 ]} Copyright 2020, The Authors, published by Wiley‐VCH. c) Schematic illustration for the construction of S13 aptamer‐modified micelles containing numbers of ferrocene (ApFA). d) The size‐changeable ApFA micelles for tumor accumulation and deep penetrating cancer therapy in response to the TME. c,d) Reproduced with permission. ^[103b] Copyright 2019, Elsevier Inc.

Figure 2

I‐motif‐based aggregatable AuNPs (Au‐GI). a) The design of Au‐GI nanoparticles and mechanism of AuNPs aggregation based on acidic pH. b) Combinatorial photothermal, photodynamic, and chemotherapy of Au‐GI for the successful eradication of triple‐negative breast cancer. a,b) Reproduced with permission.^{[ 125 ]} Copyright 2017, Wiley‐VCH.

Figure 3

a) Schematic illustration for the preparation of fol‐DNAzyme‐MnPDA nanoparticles. b) The fol‐DNAzyme‐MnPDA nanoparticles for gene‐photothermal synergistic therapy and multimode imaging. a,b) Reproduced with permission.^{[ 133 ]} Copyright 2018, American Chemical Society. c) Schematic illustration for the Mg²⁺‐dependent DNAzyme‐decorated HMMSNs synthetic process. d) The DNAzyme‐DOX@PEG/HMMSNs for responsive drug release and biodegradation. c,d) Reproduced with permission.^{[ 138 ]} Copyright 2018, Wiley‐VCH.

Figure 4

a) Schematic illustration for the synthesized route of PTX–(FdU‐integrated ASO) conjugates. b) The PTX–(FdU‐integrated ASO) assembled micelles for reversing the sensitivity of drug‐resistant tumor cells to chemotherapeutic drugs. a,b) Reproduced with permission.^{[ 156 ]} Copyright 2020, Wiley‐VCH. c) Schematic illustration for the design and cargo release mechanism of a responsive ASO‐modified micellar nanostructure. Reproduced with permission.^{[ 161 ]} Copyright 2019, American Chemical Society.