Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC).

Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O’-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.

The cell membrane-coating strategy has opened new opportunities for the development of biomimetic and multifunctional drug delivery platforms. Recently, a variety of gold nanoparticles, which can combine with blood cell membranes, have been shown to provide an effective approach for cancer therapy. Meanwhile, this class of hybrid nanostructures can deceive the immunological system to exhibit synergistic therapeutic effects. Here, we synthesized red blood cell (RBC) and platelet membrane-coated gold nanostars containing curcumin (R/P-cGNS) and evaluated whether R/P-cGNS had improved anticancer efficacy. We also validated a controlled release profile under near-infrared irradiation for the ability to target melanoma cells and to have an immunomodulatory effect on macrophages. RBC membrane coating provided self-antigens; therefore, it could evade clearance by macrophages, while platelet membrane coating provided targetability to cancer cells. Additionally, the nutraceutical curcumin provided anticancer and anti-inflammatory effects. In conclusion, the results presented in this study demonstrated that R/P-cGNS can deliver drugs to the target region and enhance anticancer effects while avoiding macrophage phagocytosis. We believe that R/P-cGNS can be a new design of the cell-based hybrid system for effective cancer therapy.

Designing new drug delivery systems (DDSs) for safer cancer therapy during pre-clinical and clinical applications still constitutes a considerable challenge, despite advances made in related fields. Lipid-based drug delivery systems (LBDDSs) have emerged as biocompatible candidates that overcome many biological obstacles. In particular, a combination of the merits of lipid carriers and functional polymers has maximized drug delivery efficiency. Functionalization of LBDDSs enables the accumulation of anti-cancer drugs at target destinations, which means they are more effective at controlled drug release in tumor microenvironments (TMEs). This review highlights the various types of ligands used to achieve tumor-specific delivery and discusses the strategies used to achieve the effective release of drugs in TMEs and not into healthy tissues. Moreover, innovative recent designs of LBDDSs are also described. These smart systems offer great potential for more advanced cancer therapies that address the challenges posed in this research area.

Cancer theranosis is an emerging field of personalized medicine which enables individual anti-cancer treatment by monitoring the therapeutic responses of cancer patients. Based on a consideration of the nano-bio interactions related to the blood circulation of systemically administered nanoparticles in humans, as well as extravasation and active targeting, lipid micellar nanoparticles were co-loaded with paclitaxel (PTX) and quantum dots (QDs) to generate a theranostic delivery vehicle. To provide with a tumor-targeting capability, either an antibody or an aptamer against the epidermal growth factor receptor (EGFR) was conjugated to the micelle surface. The QD-containing micelles (QDMs), antibody-coupled QDMs (immuno-QDMs), and aptamer-coupled QDMs (aptamo-QDMs) were able to effectively circulate in blood for at least 8 h when administered intravenously into mice bearing EGFR-positive LS174T tumor xenografts. In vivo fluorescence imaging and a bio-distribution study showed that both the immuno-QDMs and aptamo-QDMs were largely localized in the tumor tissue. The tumor targeting capability enhanced the therapeutic efficacy of PTX for the target cancer cells. Both the immuno-PTX-QDMs and the aptamo-PTX-QDMs caused a stronger inhibition of LS174T tumor growth in mice, compared to the non-targeted PTX-QDMs. These results suggest that the anti-EGFR immuno-PTX-QDMs and anti-EGFR aptamo-PTX-QDMs could be utilized as a tumor-targeted theranostic delivery system for cancer treatment in the clinic.