Aptamer-Functionalized Gold Nanoparticles As Photoresponsive Nanoplatform for Co-Drug Delivery

Abstract

Various platforms have been developed as innovative nanocarriers to deliver therapeutic agents to the diseased sites. Multifunctional surface modification allows an enhanced recognition and uptake of drug carriers by targeted cells. However, the development of drug resistance in some tumor cells plays a major role in the failure of chemotherapy. Drugs given in combination, called multidrug delivery approach, was designed to improve the therapeutic efficacy and has become an increasingly used strategy that is of great importance in clinical cancer treatments. In this study, aptamer-functionalized gold nanoparticles (Au NPs) have been used as a nanoplatform to codeliver two different anticancer drugs for improving the drug effectiveness. The surface of Au NPs (13 nm in diameter) was assembled with AS1411 aptamers, which tethered with 21-base pairs of (CGATCGA)3 sequence approached to the Au NPs. Both the photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) and the chemotherapeutic drug doxorubicin (Dox) were then physically attached to the AS1411-conjugated Au NPs (T/D:ds-NPs) and delivered to the target tumor cells such as HeLa and Dox-resistant MCF-7R cell lines. When exposed to a 632 nm light, reactive oxygen species induced by TMPyP4 molecules were generated inside the living cells, followed by cell damage. In addition, triggered release of the complementary drugs also occurred simultaneously during the photodynamic reaction. In the presence of Dox molecules, the toxicity toward the target cells was superior to individual drug treatment. Overall, a co-drug delivery platform was successfully established to improve the therapeutic efficacy in tumor cells. The improvement of the photodynamic-stimulated triggered release was enhanced, thus highly promising precise drug release in targeted drug delivery.

Gold nanoparticles enlighten the future of cancer theranostics

“…Targeting ligands [56][57][58][59][60] may be modified onto the AuNP surface to specifically deliver therapeutic cargos into tissues and organs. Recently, tumor-targeted mesoporous silicaencapsulated GNRs (GNRs@mSiO 2 ) for chemotherapy and photothermal therapy (PTT) have been developed by Shen et al 61 In this study, RGD peptides, a targeting ligand for α v β 3 integrin receptors that are known to overexpress on several cancer cells, were conjugated to the terminal groups of PEG on GNRs@mSiO 2 (namely, pGNRs@mSiO 2 -RGD).…”

Cell-targeting aptamers act as intracellular delivery vehicles

“…This composition was shown to have more than a 4-fold higher action. In another study, aptamer-functionalized GNPs were codelivered with two different anticancer drugs, achieving an improvement in drug efficacy (Shiao et al 2014). Huang et al (2008) demonstrated that ∼80 aptamers could be linked covalently to the surface of Au-Ag nanorods using thiolated functional groups on the aptamers.…”

Gold nanoparticles for cancer theranostics — A brief update

“…AS1411 functionalized AuNPs have been applied to targeted deliver chemotherapeutic doxorubicin in tumor tissues where exist higher concentrations of reductive agents such as glutathione than normal ones for increasing release of drugs, and subsequently reducing cell viability of breast cancer, cervical cancer and uveal melanoma cell lines. 53,54 Anti-His and anti-GST aptamers conjugated to citrate reduced AuNPs are able to selectively deliver various His or GST tagged proteins into varieties of cell types in vitro and in vivo for protein based tumor treatment. 55 Meanwhile, the aptamer functionalized platform for drug delivery still can combine with other methods to improve the e±cacy of chemotherapy.…”