Advances in local and systemic drug delivery systems for post-surgical cancer treatment.

Surgery is considered to be the favored approach for the treatment of most solid tumor malignancies. The quality of life among cancer patients has significantly improved due to advancements in instrumentation and surgical techniques; however, the recurrence of tumors and metastasis after operation remains challenging and results in a decreased quality of life and an increase in the mortality rate. Therefore, there is a need to explore applicable approaches to eradicate the circulating tumor cells and any residual tumor at the surgical site to inhibit the recurrence of the tumor and reduce the threat of distant metastasis. Recently drug delivery systems have been used to deliver immunotherapy or chemotherapy agents, which could augment the efficacy of surgical resection. In this review, we have summarized the efficacy and the recent progress of controlled drug delivery systems based approaches for post-surgical cancer treatment. Clinical translation challenges and opportunities have also been discussed.

Doxorubicin-Conjugated Innovative 16-mer DNA Aptamer-Based Annexin A1 Targeted Anti-Cancer Drug Delivery.

Aptamers are small, functional single-stranded DNA or RNA oligonucleotides that bind to their targets with high affinity and specificity. Experimentally, aptamers are selected by the systematic evolution of ligands by exponential enrichment (SELEX) method. Here, we have used rational drug designing and bioinformatics methods to design the aptamers, which involves three different steps. First, finding a probable aptamer-binding site, and second, designing the recognition and structural parts of the aptamers by generating a virtual library of sequences, selection of specific sequence via molecular docking, molecular dynamics (MD) simulation, binding energy calculations, and finally evaluating the experimental affinity. Following this strategy, a 16-mer DNA aptamer was designed for Annexin A1 (ANXA1). In a direct binding assay, DNA1 aptamer bound to the ANXA1 with dissociation constants value of 83 nM. Flow cytometry and fluorescence microscopy results also showed that DNA1 aptamer binds specifically to A549, HepG2, U-87 MG cancer cells that overexpress ANXA1 protein, but not to MCF7 and L-02, which are ANXA1 negative cells. We further developed a novel system by conjugating DNA1 aptamer with doxorubicin and its efficacy was studied by cellular uptake and cell viability assay. Also, anti-tumor analysis showed that conjugation of doxorubicin with aptamer significantly enhances targeted therapy against tumors while minimizing overall adverse effects on mice health.