In many therapeutic areas, current treatments involve significant side effects. Combining drug compounds with affinity agents that target specific cell surface receptors can dramatically reduce off-target effects and improve treatment effectiveness. In several studies, aptamer-mediated drug delivery has reduced toxicity and improved drug performance.

Aptamer Advantages

While antibodies are popular affinity agents, antibody-drug conjugates have some limitations due to large antibody size and immunogenicity. Development of antibody-drug conjugates is expensive and requires a long lead time. Batch-to-batch reproducibility of antibodies is sometimes a concern. Due to their small size, aptamers can better penetrate tissues and cells and have low immunogenicity in vivo. (Learn more about aptamers.) They can be easily conjugated without affecting affinity or selectivity. Because aptamers are chemically synthesized, there are no concerns regarding biological contamination or long-term reagent supply. Aptamers can be selected for binding to non-immunogenic small molecules or binding to a cell type of interest, without prior knowledge of a specific cell surface target.5 (Read more about selecting aptamers to cells.)

cMet Targeting in Chemotherapy

Researchers in Germany selected aptamers that bind the hepatocyte growth factor receptor cMet for targeted delivery of the chemotherapy drug doxorubicin to tumor cells. They combined lipidated aptamers for cell targeting and drug loading and incorporated a photoswitch to trigger drug release. The lipidized aptamers showed increased resistance to nuclease degradation and improved cellular uptake in vitro. The brief application of low-intensity UV irradiation led to 80% cell mortality in just 8 hours, while the non-irradiated control reached 57% mortality after 24 hours and 80% cell mortality after 48 hours. The team confirmed selective targeting, effective cell uptake and triggered release of drug through imaging and flow cytometry.3

Prostate Cancer Cell Targeting

Researchers at Duke University selected for aptamers that are internalized into prostate cancer cells without affecting normal prostate cells. Anti-prostate cancer cell aptamer E6 was then conjugated to the highly toxic auristatin drugs MMAE and MMAF. In vitro, the aptamer-drug conjugates selectively killed prostate cancer cells. Addition of a complementary oligonucleotide to the aptamer prevented aptamer-drug targeting and internalization, providing an effective fail-safe in the event of drug accumulation or toxicity. The E3 aptamer-MMAF drug conjugate had a half-life of 18 hours in mouse serum. In vivo administration in a mouse prostate cancer model inhibited tumor growth and increased survival.2

PDGFRβ Targeting in Glioblastoma

A team of researchers from Italy and Luxembourg developed an aptamer-drug conjugate that penetrates the blood-brain barrier for the treatment of glioblastoma. Due to expression of PDGFRβ on tumorigenic glioblastoma stem cells and resistant glioblastomas, an anti-PDGFRβ aptamer was selected for targeting. Drug was entrapped in the lipophilic portion of biodegradable polymeric nanoparticles (PNPs). RNA aptamer to PDGFRβ was then conjugated to the PNPs. Entrapment of the low solubility drug candidate in the PNPs increased its bioavailability, resulting in a 1,000-fold increase in cytotoxicity compared to the free drug. Aptamer-PNPs crossed the blood-brain barrier and accumulated at the tumor site. In vivo studies demonstrated specific glioblastoma tumor uptake and reduction in tumor marker expression in cancer-bearing mice following five days of daily intravenous administration.1

Nucleolin Targeting in Chemotherapy

Researchers from Harvard, UCSB, NC-State, and Stanford developed a peptide-aptamer system for targeted delivery of doxorubicin (DOX) and camptothecin (CPT) to nucleolin-expressing tumor cells. The team observed in vivo efficacy of the aptamer-peptide-DOX-CPT complex at 500ug/kg/dose of Dox and 350 ug/kg/dose of CDP. This was 20- to 30-fold lower than the maximum tolerated dose (MTD) for free drugs. No changes in body weight or signs of toxicity to major organs were observed. The aptamer conjugate showed a 58% reduction in tumor size vs. co-administration of DOX and CPT. It was confirmed that the aptamer conjugate entered cells via nucleolin-mediated endocytosis.4

Custom Aptamer Selection with Base Pair

Whether you have a cell type of interest or have identified a specific cell surface target, the first step in aptamer-mediated drug delivery is discovery of selective aptamers. Base Pair has discovered aptamers to cells, cell surface markers, small molecule drugs and drug metabolites. Base Pair’s patented multiplex selection enables simultaneous discovery of selective aptamers to a panel of positive and negative targets, reducing the overall time and cost of aptamer discovery and improving aptamer selectivity. Contact Base Pair to learn more.


  1. Monaco, I., et al. Aptamer functionalization of nanosystems for glioblastoma targeting through the blood-brain barrier. Journal of Medicinal Chemistry. 60:4510-4516. 2017. 
  2. Powell Gray, B., et al. Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer. PNAS. 2018. 
  3. Prusty, D.K., et al. Supramolecular aptamer constructs for receptor-mediated targeting and light-triggered release of chemotherapeutics into cancer cells. Nature Communications. 2018. 9:535. 
  4. Pusuluri, A., et al. Treating tumors at low drug doses using an aptamer-peptide synergistic drug conjugate . Angewandte Chemie International Edition. 2019. 58(5):1437-1441.
  5. Wen, J., et al. A unique aptamer-drug conjugate for targeted therapy of multiple myeloma. Leukemia. 2016. 30: 987–991.