Polymer Nanoparticles and Nanomotors Modified by DNA/RNA Aptamers and Antibodies in Targeted Therapy of Cancer
TL;DR: In this paper, a review of the recent achievements in the development of polymer nanoparticles and nano/micromotors modified by antibodies and nucleic acid aptamers is presented.
Abstract: Polymer nanoparticles and nano/micromotors are novel nanostructures that are of increased interest especially in the diagnosis and therapy of cancer. These structures are modified by antibodies or nucleic acid aptamers and can recognize the cancer markers at the membrane of the cancer cells or in the intracellular side. They can serve as a cargo for targeted transport of drugs or nucleic acids in chemo- immuno- or gene therapy. The various mechanisms, such as enzyme, ultrasound, magnetic, electrical, or light, served as a driving force for nano/micromotors, allowing their transport into the cells. This review is focused on the recent achievements in the development of polymer nanoparticles and nano/micromotors modified by antibodies and nucleic acid aptamers. The methods of preparation of polymer nanoparticles, their structure and properties are provided together with those for synthesis and the application of nano/micromotors. The various mechanisms of the driving of nano/micromotors such as chemical, light, ultrasound, electric and magnetic fields are explained. The targeting drug delivery is based on the modification of nanostructures by receptors such as nucleic acid aptamers and antibodies. Special focus is therefore on the method of selection aptamers for recognition cancer markers as well as on the comparison of the properties of nucleic acid aptamers and antibodies. The methods of immobilization of aptamers at the nanoparticles and nano/micromotors are provided. Examples of applications of polymer nanoparticles and nano/micromotors in targeted delivery and in controlled drug release are presented. The future perspectives of biomimetic nanostructures in personalized nanomedicine are also discussed.
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TL;DR: In this paper, the authors reviewed the application of polymer nanoparticles in drug delivery, gene therapy, and early diagnostics for cancer therapy, which is one of the most innovative methods of non-invasive drug delivery.
Abstract: Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.
24 citations
TL;DR: In this paper, the current trends in development of immuno-and aptasensors for various foodborne pathogens are analyzed and compared together with existing conventional methods of bacteria detection, the sensitivity of biosensor, possibility of regeneration and application in food and drinking water samples are presented.
22 citations
TL;DR: Thermoresponsive DDSs aid in making the drugs more bioavailable, enhance the therapeutic index and pharmacokinetic trends, and provide the spatial placement and temporal delivery of the drug into localized anatomical sites.
Abstract: Temperature excursions within a biological milieu can be effectively used to induce drug release from thermosensitive drug-encapsulating nanoparticles. Oncological hyperthermia is of particular interest, as it is proven to synergistically act to arrest tumor growth when combined with optimally-designed smart drug delivery systems (DDSs). Thermoresponsive DDSs aid in making the drugs more bioavailable, enhance the therapeutic index and pharmacokinetic trends, and provide the spatial placement and temporal delivery of the drug into localized anatomical sites. This paper reviews the fundamentals of thermosensitive polymers, with a particular focus on thermoresponsive liposomal-based drug delivery systems.
19 citations
TL;DR: This work summarized recent advances in biomimetic exosomes over the past decades and addressed the opportunities and challenges of the next-generation drug delivery system.
Abstract: Most of the naked drugs, including small molecules, inorganic agents, and biomacromolecule agents, cannot be used directly for disease treatment because of their poor stability and undesirable pharmacokinetic behavior. Their shortcomings might seriously affect the exertion of their therapeutic effects. Recently, a variety of exogenous and endogenous nanomaterials have been developed as carriers for drug delivery. Among them, exosomes have attracted great attention due to their excellent biocompatibility, low immunogenicity, low toxicity, and ability to overcome biological barriers. However, exosomes used as drug delivery carriers have significant challenges, such as low yields, complex contents, and poor homogeneity, which limit their application. Engineered exosomes or biomimetic exosomes have been fabricated through a variety of approaches to tackle these drawbacks. We summarized recent advances in biomimetic exosomes over the past decades and addressed the opportunities and challenges of the next-generation drug delivery system.
14 citations
TL;DR: This review highlights the state of the field, current challenges in delivery, and opportunities for engineered nanomaterials to meet these challenges, including enabling long‐term therapeutic gene editing.
Abstract: Genetic medicine has great potential to treat the underlying causes of many human diseases with exquisite precision, but the field has historically been stymied by delivery as the central challenge. Nanoparticles, engineered constructs the size of natural viruses, are being designed to more closely mimic the delivery efficiency of viruses, while enabling the advantages of increased safety, cargo‐carrying flexibility, specific targeting, and ease in manufacturing. The speed in which nonviral gene transfer nanoparticles are making progress in the clinic is accelerating, with clinical validation of multiple nonviral nucleic acid delivery nanoparticle formulations recently FDA approved for both expression and for silencing of genes. While much of this progress has been with lipid nanoparticle formulations, significant development is being made with other nanomaterials for gene transfer as well, with favorable attributes such as biodegradability, scalability, and cell targeting. This review highlights the state of the field, current challenges in delivery, and opportunities for engineered nanomaterials to meet these challenges, including enabling long‐term therapeutic gene editing. Delivery technology utilizing different kinds of nanomaterials and varying cargos for gene transfer (DNA, mRNA, and ribonucleoproteins) are discussed. Clinical applications are presented, including for the treatment of genetic diseases such as cystic fibrosis.
12 citations
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TL;DR: High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species.
Abstract: High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.
9,367 citations
TL;DR: Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules.
Abstract: Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 10(10) random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands.
8,781 citations
TL;DR: Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats, and may play a key role either in conjunction with, or in place of, antibodies in the form of aptamer-based diagnostic products in the market.
Abstract: Antibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have made substantial contributions toward the advancement of diagnostic assays and have become indispensable in most diagnostic tests that are used routinely in clinics today. The development of the systematic evolution of ligands by exponential enrichment (SELEX) process, however, made possible the isolation of oligonucleotide sequences with the capacity to recognize virtually any class of target molecules with high affinity and specificity. These oligonucleotide sequences, referred to as "aptamers", are beginning to emerge as a class of molecules that rival antibodies in both therapeutic and diagnostic applications. Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats. The demand for diagnostic assays to assist in the management of existing and emerging diseases is increasing, and aptamers could potentially fulfill molecular recognition needs in those assays. Compared with the bellwether antibody technology, aptamer research is still in its infancy, but it is progressing at a fast pace. The potential of aptamers may be realized in the near future in the form of aptamer-based diagnostic products in the market. In such products, aptamers may play a key role either in conjunction with, or in place of, antibodies. It is also likely that existing diagnostic formats may change according to the need to better harness the unique properties of aptamers.
2,178 citations
TL;DR: It is demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates, and patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy.
Abstract: There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor. One hallmark of UBC is the presence of high rates of somatic mutations. These alterations may enhance the ability of the host immune system to recognize tumour cells as foreign owing to an increased number of antigens. However, these cancers may also elude immune surveillance and eradication through the expression of programmed death-ligand 1 (PD-L1; also called CD274 or B7-H1) in the tumour microenvironment. Therefore, we examined the anti-PD-L1 antibody MPDL3280A, a systemic cancer immunotherapy, for the treatment of metastatic UBC. MPDL3280A is a high-affinity engineered human anti-PD-L1 monoclonal immunoglobulin-G1 antibody that inhibits the interaction of PD-L1 with PD-1 (PDCD1) and B7.1 (CD80). Because PD-L1 is expressed on activated T cells, MPDL3280A was engineered with a modification in the Fc domain that eliminates antibody-dependent cellular cytotoxicity at clinically relevant doses to prevent the depletion of T cells expressing PD-L1. Here we show that MPDL3280A has noteworthy activity in metastatic UBC. Responses were often rapid, with many occurring at the time of the first response assessment (6 weeks) and nearly all were ongoing at the data cutoff. This phase I expansion study, with an adaptive design that allowed for biomarker-positive enriched cohorts, demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates. Moreover, owing to the favourable toxicity profile, including a lack of renal toxicity, patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy. These results suggest that MPDL3280A may have an important role in treating UBC-the drug received breakthrough designation status by the US Food and Drug Administration (FDA) in June 2014.
2,101 citations
TL;DR: In this paper, an attempt was made to elucidate the mechanisms of formation in terms of interfacial turbulence between two unequilibrated liquid phases involving flow, diffusion and surface tension decrease (Marangoni effect).
2,017 citations