Aptamer mediated targeted delivery of cancer therapeutics
The major challenges of cancer research include finding ways to maximize the tolerated dose of chemotherapeutic drug given and balancing this with an acceptable toxicity profile. One promising approach is to transport drugs to their specific target destinations by increasing the selectivity to cancerous cells. This in turn, can shield the drugs from elimination and degradation in the process of overcoming biological barriers.
This can only be achieved by the combination of targeted drug delivery and controlled release of chemotherapeutic drugs, providing the optimum dosage for long periods that will increase the efficacy of the therapy. Aptamers have become a promising targeting tool in the development of targeted drug delivery system because of their unique binding properties that prove them advantageous over antibodies such as:
- Enhanced biostability for clinical applications
- Easy chemical modifications that allow different conjugation chemistries
- Low immunogenicity
- Small size for better tissue penetration
- Less batch to batch variation
- Ease of synthesis
Based on the benefits of aptamers, increasing attention has been presented in utilizing them as targeted ligands for cancer drug delivery. The approach of such target drug delivery typically consist of three major components:
- Anticancer drugs
- Drug carrier in the form of nanoparticle or nanostructure (nanoparticle or liposome)
- Tumour targeting ligand conjugated to the carrier (aptamer)
Recently, progress of the aptamer-targeted approach has presented new therapeutic systems for several types of cancer, with decreased toxicity and improved efficacy. This review highlights two of such promising approaches of aptamer-mediated targeted drug delivery to cancer cells in vitro and in vivo.
Aptamer mediated targeted therapy for colon cancer
Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted drug delivery is an important strategy to reduce the adverse effects. Yao et al., 2020 designed and fabricated a novel drug delivery system consisting of a self-assembled DNA nano-cross (Holiday junction, HJ) functionalized with four AS1411 aptamers (Apt-HJ) that was loaded with Doxorubicin (Apt-HJ-Dox) for targeted delivery of Dox to colon cancer cells. Phosphorothioate modification was used to enhance the nuclease resistance of aptamers.
Confocal microscopy revealed that the complex selectively delivered Dox into target CT26 colon cancer cells and not to the control CHO cells . Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced damage to control cells. In vivo analysis showed that antitumor efficacy was enhanced significantly by the complex Apt-HJ-Dox as compared to the free Dox alone. Moreover, there was no further weight loss indicating that the complex did not generate extra systemic toxicity while enhancing the therapeutic efficacy.
Aptamer mediated targeted therapy for prostate cancer
Prostrate cancer (PC) is the most common type of diagnosed malignancy in men, accounting for nearly 30 % of all cancers. Combined chemotherapy has been shown to be an effective strategy for the treatment of PC therapy. Chen et al.,2020 synthesized and evaluated synergistic potential of an aptamer (A10-3.2) functionalized with two drugs, curcumin (CUR) and cabazitaxel (CTX), which was co-delivered with lipid-polymer hybrid nanoparticles (LPNs) for anti-prostrate cancer therapy. The aptamer-mediated complex together was called APT-CUR/ CTX-LPNs.
The cellular uptake efficiency of the aptamer-mediated complex was higher in the target LNCaP cells as compared to the control PC3 cells. The drug release from the complex was slower than that of CUR/CTX-LPNs, indicating that the aptamer covered on the surface acted as a molecular fence that helped to retain the drugs inside the NPs. The complex also exhibited good cell inhibition ability, higher tumour accumulation and remarkable tumour inhibition efficiency at the drug ratio of 2:5 (CUR: CTX). Overall, the APT-CUR/ CTX-LPNs complex offered a great promise for the double drugs delivery to the prostrate cancer cells and tumour xenografts in vivo, demonstrating the potential of synergistic combination therapy for prostate cancer.
Overall, the results have demonstrated that aptamer based drug delivery systems possess application potential in the development of novel chemotherapy against any form of cancer. This in turn, can maximize patient compliance and enhance the ability to use highly toxic, poorly soluble, or relatively unstable drugs.
Moreover, these aptamer-targeted systems have offered a simpler alternative to drug delivery and bypassed many of the issues faced during the development of antibody-drug conjugates (ADCs). It is also indicated that the aptamer target molecules may also provide useful information for explaining the mechanism of oncogenesis thereby paving the way for novel gene therapies.
At Aptamer Group Ltd (AGL), we offer the advantage of designing aptamers to be optimized for the conditions you want to use them in. This way they are engineered to bind to their target with high specificity and affinity. Moreover, AGL continuously aims to conduct further research in prevention, diagnosis and treatment of cancer. For example, we have developed aptamers as therapeutics agents for the treatment of Chronic Myelomonocytic Leukemia (CMML) and other myeloid malignancies (check references for the link). If you would like to know more about aptamers and their applications in diagnostics and therapeutics, please get in touch.
Chen Y, Deng Y, Zhu C, Xiang C. Anti prostate cancer therapy: Aptamer-functionalized, curcumin and cabazitaxel co-delivered, tumor targeted lipid-polymer hybrid nanoparticles. Biomed Pharmacother. 2020;127:110181. doi:10.1016/j.biopha.2020.110181
Yao F, An Y, Li X, Li Z, Duan J, Yang XD. Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin. Int J Nanomedicine. 2020;15:2119-2129. Published 2020 Mar 27. doi:10.2147/IJN.S240083