scholarly journals Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications

2019 ◽  
Vol 5 (9) ◽  
pp. eaax7946 ◽  
Author(s):  
John R. Clegg ◽  
Afshan S. Irani ◽  
Eric W. Ander ◽  
Catherine M. Ludolph ◽  
Abhijeet K. Venkataraman ◽  
...  
Keyword(s):  
Small Molecules ◽  
Precision Medicine ◽  
Photothermal Therapy ◽  
Physicochemical Characteristics ◽  
Therapeutic Modalities ◽  
Environmental Responsiveness ◽  
Methacrylic Acid Copolymers ◽  
Cross Linker ◽  
High Throughput Assay ◽  
Poly Acrylamide

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient’s disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels’ composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.

Enzyme-Instructed Self-assembly in Biological Milieu for Theranostics Purpose

2019 ◽  
Vol 26 (8) ◽  
pp. 1351-1365 ◽  
Author(s):  
Zhentao Huang ◽  
Qingxin Yao ◽  
Simin Wei ◽  
Jiali Chen ◽  
Yuan Gao
Keyword(s):  
Small Molecules ◽  
Precision Medicine ◽  
Self Assembly ◽  
Public Healthcare ◽  
Enzymatic Conversion ◽  
Vaccine Adjuvants ◽  
New Paradigm ◽  
Cancer Treatments ◽  
The Past ◽  
Biological Milieu

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.

scholarly journals Therapeutic Advances in Oncology

2021 ◽  
Vol 22 (4) ◽  
pp. 2008
Author(s):  
Jinsha Liu ◽  
Priyanka Pandya ◽  
Sepideh Afshar
Keyword(s):  
Small Molecules ◽  
New Technologies ◽  
Treatment Options ◽  
Current Treatment ◽  
Bispecific Antibodies ◽  
Gene Therapies ◽  
Therapeutic Modalities ◽  
The Past ◽  
Drug Conjugates ◽  
Novel Targets

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.

scholarly journals Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

2020 ◽  
Author(s):  
Rajdeep S. Virdi ◽  
Robert V. Bavisotto ◽  
Nicholas C. Hopper ◽  
Nemanja Vuksanovic ◽  
Trevor R. Melkonian ◽  
...  
Keyword(s):  
Small Molecules ◽  
Antiviral Drug ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Molecular Probes ◽  
Structural Protein ◽  
Beta Lactams ◽  
Autodock Vina ◽  
Differential Scanning Fluorimetry ◽  
High Throughput Assay

ABSTRACTSmall molecules that bind the SARS-CoV-2 non-structural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to coronavirus’ ability to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, beta-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using Autodock VINA. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.

scholarly journals Emerging Therapeutic Modalities against COVID-19

2020 ◽  
Vol 13 (8) ◽  
pp. 188 ◽  
Author(s):  
Shipra Malik ◽  
Anisha Gupta ◽  
Xiaobo Zhong ◽  
Theodore P. Rasmussen ◽  
Jose E. Manautou ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Therapeutic Interventions ◽  
Pharmaceutical Companies ◽  
The Novel ◽  
Comprehensive Overview ◽  
Therapeutic Modalities ◽  
Academic Researchers ◽  
Approved Drugs ◽  
Fda Approved Drugs

The novel SARS-CoV-2 virus has quickly spread worldwide, bringing the whole world as well as the economy to a standstill. As the world is struggling to minimize the transmission of this devastating disease, several strategies are being actively deployed to develop therapeutic interventions. Pharmaceutical companies and academic researchers are relentlessly working to investigate experimental, repurposed or FDA-approved drugs on a compassionate basis and novel biologics for SARS-CoV-2 prophylaxis and treatment. Presently, a tremendous surge of COVID-19 clinical trials are advancing through different stages. Among currently registered clinical efforts, ~86% are centered on testing small molecules or antibodies either alone or in combination with immunomodulators. The rest ~14% of clinical efforts are aimed at evaluating vaccines and convalescent plasma-based therapies to mitigate the disease's symptoms. This review provides a comprehensive overview of current therapeutic modalities being evaluated against SARS-CoV-2 virus in clinical trials.

scholarly journals Plant-Derived Extracellular Vesicles as Therapeutic Nanocarriers

2021 ◽  
Vol 23 (1) ◽  
pp. 191
Author(s):  
Theodora Karamanidou ◽  
Alexander Tsouknidas
Keyword(s):  
Extracellular Vesicles ◽  
Functional Materials ◽  
Physicochemical Characteristics ◽  
Eukaryotic Cell ◽  
Therapeutic Modalities ◽  
Therapeutic Delivery ◽  
Nutraceutical Compounds ◽  
Novel Applications

Mammalian exosomes have emerged as a promising class of functional materials, inspiring novel applications as therapeutic vehicles and nutraceutical compounds. Despite this, their immunogenicity has been an issue of controversy within the scientific community. Although, exosome-like vesicles, innately formed in plants and inherent to eukaryotic cell-derived vesicles, could soothe most of the concerns, they are notably underutilized as therapeutic modalities. This review highlights all efforts published so far, on the use of plant-derived extracellular vesicles (EVs) as therapeutic delivery systems. A summary of the physicochemical characteristics of plant-derived EVs is provided along with their main biological composition and in vitro/in vivo evidence of their therapeutic efficacy provided where available. Despite only a hand full of clinical trials being underway, concerning these vesicles, they arguably possess significant potential as nanodelivery systems of natural origin.

scholarly journals Low-Temperature Photothermal Therapy: Strategies and Applications

Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-38
Author(s):  
Xiulin Yi ◽  
Qiu-Yi Duan ◽  
Fu-Gen Wu
Keyword(s):  
Low Temperature ◽  
Photothermal Therapy ◽  
Combined Treatments ◽  
Excellent Performance ◽  
Cancer Treatments ◽  
Future Directions ◽  
Excessive Heat ◽  
Therapeutic Modalities ◽  
Therapy Strategies ◽  
Mild Temperature

Although photothermal therapy (PTT) with the assistance of nanotechnology has been considered as an indispensable strategy in the biomedical field, it still encounters some severe problems that need to be solved. Excessive heat can induce treated cells to develop thermal resistance, and thus, the efficacy of PTT may be dramatically decreased. In the meantime, the uncontrollable diffusion of heat can pose a threat to the surrounding healthy tissues. Recently, low-temperature PTT (also known as mild PTT or mild-temperature PTT) has demonstrated its remarkable capacity of conquering these obstacles and has shown excellent performance in bacterial elimination, wound healing, and cancer treatments. Herein, we summarize the recently proposed strategies for achieving low-temperature PTT based on nanomaterials and introduce the synthesis, characteristics, and applications of these nanoplatforms. Additionally, the combination of PTT and other therapeutic modalities for defeating cancers and the synergistic cancer therapeutic effect of the combined treatments are discussed. Finally, the current limitations and future directions are proposed for inspiring more researchers to make contributions to promoting low-temperature PTT toward more successful preclinical and clinical disease treatments.

scholarly journals Nanomedicine-enabled chemotherapy-based synergetic cancer treatments

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Wencheng Wu ◽  
Yinying Pu ◽  
Jianlin Shi
Keyword(s):  
Photothermal Therapy ◽  
Biomedical Application ◽  
Research Area ◽  
Chemotherapeutic Agents ◽  
Therapeutic Modality ◽  
Toxic Substances ◽  
Cancer Treatments ◽  
Therapeutic Modalities ◽  
Malignant Solid Tumor ◽  
Underlying Mechanisms

AbstractChemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible. Graphical Abstract

scholarly journals Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs

2020 ◽  
Vol 13 (4) ◽  
pp. 74
Author(s):  
Minoru Ishikawa ◽  
Shusuke Tomoshige ◽  
Yosuke Demizu ◽  
Mikihiko Naito
Keyword(s):  
Small Molecules ◽  
Target Proteins ◽  
Therapeutic Modalities ◽  
Selective Degradation ◽  
Apoptosis Protein ◽  
Ubiquitin Ligase E3 ◽  
Dependent Protein ◽  
Specific Proteins ◽  
Degradation Activity ◽  
Chimeric Molecules

New therapeutic modalities are needed to address the problem of pathological but undruggable proteins. One possible approach is the induction of protein degradation by chimeric drugs composed of a ubiquitin ligase (E3) ligand coupled to a ligand for the target protein. This article reviews chimeric drugs that decrease the level of specific proteins such as proteolysis targeting chimeric molecules (PROTACs) and specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs), which target proteins for proteasome-mediated degradation. We cover strategies for increasing the degradation activity induced by small molecules, and their scope for application to undruggable proteins.

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