Abstract
The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox) was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA+ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells.
Highlights
Cancer is still the number two leading cause of death, despite advances in surgery, radiotherapy, and chemotherapy treatment [1,2]
We have demonstrated that the adverse effects of doxorubicin can be significantly reduced, or even eliminated, by means of a drug delivery system developed in this work
Our experimental results indicate the remarkable death of PMSA+ prostate cancer cells, suggesting targeted doxorubicin delivery into prostate cancer cells when aptamers and NPs are used for delivery
Summary
Cancer is still the number two leading cause of death, despite advances in surgery, radiotherapy, and chemotherapy treatment [1,2]. The severity of complications from these antineoplastics is directly proportional to the dosage and administration methods [4]. To eliminate these side effects, these drugs must be delivered to targeted tumors at a minimum dose. Numerous efforts have been made so far to develop targeted drug delivery systems for cancer treatment [5,6]. The general idea for targeted drug delivery is to combine anti-cancer drugs with a molecular recognition element that can interact with tumor-associated antigens or receptors. Interaction between the added molecular recognition element and the tumor cells ensures the delivery of anti-cancer drugs elusively to tumors. With the advent of the systematic evolution of ligands through exponential enrichment procedures, a new class of targeting-capable biomolecules, i.e., aptamers, emerged [7,8]
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