4 Aptamer-Based Drug Delivery Systems
93
4.4.2.3 Poly (Lactic-Co-Glycolic Acid) (PLGA)
PLGA is an FDA approved polymer, which is used in various therapeutic drug
delivery systems. It is synthesized from the copolymerization of glycoside and
lactide. As a carrier material, PLGA has many advantages. For example, it has good
biocompatibility and can be degraded in the body. In addition, it has good film and
capsule-forming properties. Importantly, aptamers can be covalently conjugated with
PLGA nanoparticles, thus providing an excellent platform to construct targeted drug
delivery systems.
Jiao et al. [84] covalently anchored triplex-forming oligonucleotides (TFO) to
PLGA-PEG-Aptamer copolymers for cancer therapy. The system successfully downregulated androgen receptor (AR) gene’s expression at the translation stage, thus
inhibiting the growth of prostate cancer cells. Compared with the naked TFO with
no aptamer and PLGA-PEG copolymers or saline, the aptamer-carried conjugation was more efficient for cellular uptake, therefore, exhibiting enhanced inhibition to both AR gene’s expression and prostate cancer growth. In another study,
combining poly (β amino ester) (PβAE) with PLGA NPs, a targeted delivery system
was designed to deliver antimir-21 and epirubicin (Fig. 4.7a) [85]. In this system, the
PβAE polymer was electrostatically condensed with the antimir-21 as an microRNA21 inhibitor upregulated in several cancers, and then allowed electrostatic deposition of PLGA to form a reservoir for cationic drug, epirubicin. Covent modification of MUC1 aptamers enabled the PLGA NPs to be efficiently internalized into
target cells, such as MCF7 (human breast carcinoma cell) and C26 (murine colon
carcinoma cell) cell, and caused remarkable inhibition of tumor growth in mice
tumor models, and Fang et al. [86] reported an aptamer-conjugated multifunctional
polymeric nanoparticles for the treatment of castration-resistant prostate cancer.
The “core-shell” nanoparticles were self-assembled from functionalized amphiphilic
triblock copolymer composed of PLGA, PEG, and a Wy5a aptamer. This aptamer
was screened by cell-SELEX technique and it can target the CRPC cell line, PC3 cells. Anticancer drug docetaxel and hydrophobic superparamagnetic iron oxide
nanoparticle clusters were simultaneously encapsulated into the prepared nanostructure. The nanoparticles showed a controlled drug release manner and an increased
contrast-enhanced MRI capability. Both in vitro and in vivo experiments demonstrated that the surface modification of Wy5a aptamer mediated the delivery of drugs
to PC-3 cells, significantly increased cancer cell killing efficacy. The in vivo studies
revealed that the targeting nanoparticles exhibited efficacious antitumor capability
without significant systemic toxicity. Very recently, Chen et al. [87] synthesized
an aptamer conjugated, curcumin (CUR) and cabazitaxel (CTX) codelivered, lipidpolymer hybrid nanoparticles (APT-CUR/CTX-LPNs) for the treatment of prostate
cancer (PC). The A10-3.2 aptamer used in this work can specifically bind to PSMA
positive LNCaP cells and improve the internalization of LPNs. Both CUR and CTX
exhibited a sustained release from LPNs in vitro. Besides, the aptamer-functionalized
APT-CUR/CTX-LPNs represented excellent cellular inhibition efficacy, high tumor
93
4.4.2.3 Poly (Lactic-Co-Glycolic Acid) (PLGA)
PLGA is an FDA approved polymer, which is used in various therapeutic drug
delivery systems. It is synthesized from the copolymerization of glycoside and
lactide. As a carrier material, PLGA has many advantages. For example, it has good
biocompatibility and can be degraded in the body. In addition, it has good film and
capsule-forming properties. Importantly, aptamers can be covalently conjugated with
PLGA nanoparticles, thus providing an excellent platform to construct targeted drug
delivery systems.
Jiao et al. [84] covalently anchored triplex-forming oligonucleotides (TFO) to
PLGA-PEG-Aptamer copolymers for cancer therapy. The system successfully downregulated androgen receptor (AR) gene’s expression at the translation stage, thus
inhibiting the growth of prostate cancer cells. Compared with the naked TFO with
no aptamer and PLGA-PEG copolymers or saline, the aptamer-carried conjugation was more efficient for cellular uptake, therefore, exhibiting enhanced inhibition to both AR gene’s expression and prostate cancer growth. In another study,
combining poly (β amino ester) (PβAE) with PLGA NPs, a targeted delivery system
was designed to deliver antimir-21 and epirubicin (Fig. 4.7a) [85]. In this system, the
PβAE polymer was electrostatically condensed with the antimir-21 as an microRNA21 inhibitor upregulated in several cancers, and then allowed electrostatic deposition of PLGA to form a reservoir for cationic drug, epirubicin. Covent modification of MUC1 aptamers enabled the PLGA NPs to be efficiently internalized into
target cells, such as MCF7 (human breast carcinoma cell) and C26 (murine colon
carcinoma cell) cell, and caused remarkable inhibition of tumor growth in mice
tumor models, and Fang et al. [86] reported an aptamer-conjugated multifunctional
polymeric nanoparticles for the treatment of castration-resistant prostate cancer.
The “core-shell” nanoparticles were self-assembled from functionalized amphiphilic
triblock copolymer composed of PLGA, PEG, and a Wy5a aptamer. This aptamer
was screened by cell-SELEX technique and it can target the CRPC cell line, PC3 cells. Anticancer drug docetaxel and hydrophobic superparamagnetic iron oxide
nanoparticle clusters were simultaneously encapsulated into the prepared nanostructure. The nanoparticles showed a controlled drug release manner and an increased
contrast-enhanced MRI capability. Both in vitro and in vivo experiments demonstrated that the surface modification of Wy5a aptamer mediated the delivery of drugs
to PC-3 cells, significantly increased cancer cell killing efficacy. The in vivo studies
revealed that the targeting nanoparticles exhibited efficacious antitumor capability
without significant systemic toxicity. Very recently, Chen et al. [87] synthesized
an aptamer conjugated, curcumin (CUR) and cabazitaxel (CTX) codelivered, lipidpolymer hybrid nanoparticles (APT-CUR/CTX-LPNs) for the treatment of prostate
cancer (PC). The A10-3.2 aptamer used in this work can specifically bind to PSMA
positive LNCaP cells and improve the internalization of LPNs. Both CUR and CTX
exhibited a sustained release from LPNs in vitro. Besides, the aptamer-functionalized
APT-CUR/CTX-LPNs represented excellent cellular inhibition efficacy, high tumor