Using nanoparticles to carry and delivery anticancer drugs holds much promise in cancer therapy, but nanoparticles per se are lacking specificity. Active targeting, that is, using specific ligands to functionalize nanoparticles, is attracting much attention in recent years. Aptamers, with their several favorable features like high specificity and affinity, small size, very low immunogenicity, relatively low cost for production, and easiness to store, are one of the best candidates for the specific ligands of nanoparticle functionalization. This review discusses the benefits and challenges of using aptamers to functionalize nanoparticles for active targeting and especially presents nearly all of the published works that address the topic of using aptamers to functionalize nanoparticles for targeted drug delivery and cancer therapy.

The arrival of the monoclonal antibody (mAb) technology in the 1970s brought with it the hope of conquering cancers to the medical community. However, mAbs, on the whole, did not achieve the expected wonder in cancer therapy although they do have demonstrated successfulness in the treatment of a few types of cancers. In 1990, another technology of making biomolecules capable of specific binding appeared. This technique, systematic evolution of ligands by exponential enrichment (SELEX), can make aptamers, single-stranded DNAs or RNAs that bind targets with high specificity and affinity. Aptamers have some advantages over mAbs in therapeutic uses particularly because they have little or no immunogenicity, which means the feasibility of repeated use and fewer side effects. In this review, the general properties of the aptamer, the advantages and limitations of aptamers, the principle and procedure of aptamer production with SELEX, particularly the undergoing studies in aptamers for cancer therapy, and selected anticancer aptamers that have entered clinical trials or are under active investigations are summarized.

CD8⁺ cytotoxic T lymphocyte (CTL) protects against infection and cancer cells. Understanding the mechanisms involved in generation and maintenance of effective CTL responses is essential for improving disease therapy and vaccine protocols. During CTL responses, immune cells encounter several tightly regulated signaling pathways; therefore, in such a dynamic process, proper integration of critical signals is necessary to orchestrate an effective immune response. In this review, we have focused on CD40–CD40L interactions (a key signal) in the regulation of dendritic cell (DC)–T cell (CD4⁺ T and CD8⁺ T) cross-talk, rescuing CTL exhaustion, and converting DC tolerization. We have also highlighted the knowledge gap and future directions to design immunotherapies.

Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases. We demonstrate that SMG inhibits NADH induction and glycolysis, but induces mitochondrial biogenesis. Interestingly, administration of a RhoA activator, the cytotoxic necrotizing factor-1 (CNF1) effectively converts SMG-triggered alterations and effects on mitochondria biogenesis or glycolysis. CNF1 also converts the SMG-altered cell proliferation and tumor metastasis. In contrast, mTORC inhibitor, rapamycin, produces opposite responses and mimics SMG-induced effects in cells at normal gravity. Taken together, our observations indicate that SMG inhibits focal adhesions, leading to inhibition of signaling FAK and RhoA, and the mTORC1 pathway, which results in activation of the AMPK pathway and reduced melanoma cell proliferation and metastasis. Overall, our findings shed a new light on effects of microgravity on cell biology and human health.

Simulated-microgravity (SMG) promotes cell-apoptosis. We demonstrated that SMG inhibited cell proliferation/metastasis via FAK/RhoA-regulated mTORC1 pathway. Since mTORC1, NF-κB, and ERK1/2 signaling are important in cell apoptosis, we examined whether SMG-enhanced apoptosis is regulated via these signals controlled by FAK/RhoA in BL6-10 melanoma cells under clinostat-modelled SMG-condition. We show that SMG promotes cell-apoptosis, alters cytoskeleton, reduces focal adhesions (FAs), and suppresses FAK/RhoA signaling. SMG down-regulates expression of mTORC1-related Raptor, pS6K, pEIF4E, pNF-κB, and pNF-κB-regulated Bcl2, and induces relocalization of pNF-κB from the nucleus to the cytoplasm. In addition, SMG also inhibits expression of nuclear envelope proteins (NEPs) lamin-A, emerin, sun1, and nesprin-3, which control nuclear positioning, and suppresses nuclear positioning-regulated pERK1/2 signaling. Moreover, rapamycin, the mTORC1 inhibitor, also enhances apoptosis in cells under 1 g condition via suppressing the mTORC1/NF-κB pathway. Furthermore, the FAK/RhoA activator, toxin cytotoxic necrotizing factor-1 (CNF1), reduces cell apoptosis, restores the cytoskeleton, FAs, NEPs, and nuclear positioning, and converts all of the above SMG-induced changes in molecular signaling in cells under SMG. Therefore, our data demonstrate that SMG reduces FAs and alters the cytoskeleton and nuclear positioning, leading to enhanced cell apoptosis via suppressing the FAK/RhoA-regulated mTORC1/NF-κB and ERK1/2 pathways. The FAK/RhoA regulatory network may, thus, become a new target for the development of novel therapeutics for humans under spaceflight conditions with stressed physiological challenges, and for other human diseases.