Ultrasensitive Detection of Vitamin E by Signal Conversion Combined with Core-satellite Structure-based Plasmon Coupling Effect

Rapidly and sensitively surface-enhanced Raman scattering (SERS) detection of molecular biomarkers from real samples is still a challenge, because the intrinsically trace analytes may have a low molecular affinity for...

Quantitative Surface-Enhanced Spectroscopy

Surface-enhanced Raman scattering (SERS), a powerful technique for trace molecular detection, depends on chemical and electromagnetic enhancements. While recent advances in instrumentation and substrate design have expanded the utility, reproducibility, and quantitative capabilities of SERS, some challenges persist. In this review, advances in quantitative SERS detection are discussed as they relate to intermolecular interactions, surface selection rules, and target molecule solubility and accessibility. After a brief introduction to Raman scattering and SERS, impacts of surface selection rules and enhancement mechanisms are discussed as they relate to the observation of activation and deactivation of normal Raman modes in SERS. Next, experimental conditions that can be used to tune molecular affinity to and density near SERS substrates are summarized and considered while tuning these parameters are conveyed. Finally, successful examples of quantitative SERS detection are discussed, and future opportunities are outlined. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Biomimetic Nanotechnology: A Natural Path Forward for Tumor-Selective and Tumor-Specific NIR Activable Photonanomedicines

The emergence of biomimetic nanotechnology has seen an exponential rise over the past decade with applications in regenerative medicine, immunotherapy and drug delivery. In the context of nanomedicines activated by near infrared (NIR) photodynamic processes (photonanomedicines; PNMs), biomimetic nanotechnology is pushing the boundaries of activatable tumor targeted nanoscale drug delivery systems. This review discusses how, by harnessing a unique collective of biological processes critical to targeting of solid tumors, biomimetic PNMs (bPNMs) can impart tumor cell specific and tumor selective photodynamic therapy-based combination regimens. Through molecular immune evasion and self-recognition, bPNMs can confer both tumor selectivity (preferential bulk tumor accumulation) and tumor specificity (discrete molecular affinity for cancer cells), respectively. They do so in a manner that is akin, yet arguably superior, to synthetic molecular-targeted PNMs. A particular emphasis is made on how bPNMs can be engineered to circumvent tumor cell heterogeneity, which is considered the Achilles’ heel of molecular targeted therapeutics. Forward-looking propositions are also presented on how patient tumor heterogeneity can ultimately be recapitulated to fabricate patient-specific, heterogeneity-targeting bPNMs.

Towards Smart Drug Delivery: Exploration Of A Molecularly Imprinted Polymer Network

The current study explores the concept of Molecular Imprinting Technology (MIT) and evaluates the ability of a molecularly imprinted hydrogel polymer (MIP) to preferentially uptake the template drug propranolol from aqueous solution. The extent of the molecular affinity and recognition was challenged by introducing a secondary competing structure during uptake. The release of propranolol as a response to environmental stimuli was investigated. The MIP was synthesized with copolymers methyl methacrylate (MMA) and N,N-dimethyl acrylamide (DMAA). Morphology was studied by scanning electron microscopy (SEM), ptake, displacement, and release experiments were studied by fluorescence spectroscopy. The SEM studies did not indicate the presence of molecularly imprinted cavities. The MIPs demonstrated preferential uptake in comparison to the non-imprinted (NIP) counterpart. The displacement studies revealed that uptake by the MIP is not very selective. The release studies demonstrated that ropranolol release can be tailored to respond to environmental stimuli such as temperature and, especially, pH.

Towards Smart Drug Delivery: Exploration Of A Molecularly Imprinted Polymer Network

The current study explores the concept of Molecular Imprinting Technology (MIT) and evaluates the ability of a molecularly imprinted hydrogel polymer (MIP) to preferentially uptake the template drug propranolol from aqueous solution. The extent of the molecular affinity and recognition was challenged by introducing a secondary competing structure during uptake. The release of propranolol as a response to environmental stimuli was investigated. The MIP was synthesized with copolymers methyl methacrylate (MMA) and N,N-dimethyl acrylamide (DMAA). Morphology was studied by scanning electron microscopy (SEM), ptake, displacement, and release experiments were studied by fluorescence spectroscopy. The SEM studies did not indicate the presence of molecularly imprinted cavities. The MIPs demonstrated preferential uptake in comparison to the non-imprinted (NIP) counterpart. The displacement studies revealed that uptake by the MIP is not very selective. The release studies demonstrated that ropranolol release can be tailored to respond to environmental stimuli such as temperature and, especially, pH.

Paclitaxel loading in cationic liposome vectors is enhanced by replacement of oleoyl with linoleoyl tails with distinct lipid shapes

Lipid carriers of hydrophobic paclitaxel (PTX) are used in clinical trials for cancer chemotherapy. Improving their loading capacity requires enhanced PTX solubilization. We compared the time-dependence of PTX membrane solubility as a function of PTX content in cationic liposomes (CLs) with lipid tails containing one (oleoyl; DOPC/DOTAP) or two (linoleoyl; DLinPC/newly synthesized DLinTAP) cis double bonds by using microscopy to generate kinetic phase diagrams. The DLin lipids displayed significantly increased PTX membrane solubility over DO lipids. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the solubility limit, which has been the focus of most previous studies and clinical trials) in DOTAP/DOPC CLs. The increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX, rather than by the transition in membrane structure from bilayers to inverse cylindrical micelles observed with small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against prostate cancer cells (their IC50 of PTX cytotoxicity) was unaffected by changing the lipid tails, and toxicity of the CL carrier was negligible. Moreover, efficacy was approximately doubled against melanoma cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. Our findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.

DFT, Molecular Docking, and ADME/Tox Screening Investigations of Market‑Available Drugs against SARS‑CoV‑2

A series of drugs was investigated to determine structural, electronic and pharmacological properties, as well as the molecular affinity for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). The drugs were submitted to density functional theory calculations to optimize structures and predict binding preferences. The optimized geometries were used in molecular docking simulations. In the docking study, the receiver was considered rigid and the drugs flexible. The Lamarckian genetic algorithm with global search and Pseudo-Solis and Wets with local search were adopted for docking. Absorption, distribution, metabolism, excretion and toxicological properties were obtained from the Pre-ADMET online server. In this series, the antiviral atazanavir showed the potential to inhibit the main protease of SARS‑CoV‑2, based on the free binding energy, inhibition constant, binding interactions and its favorable pharmacological properties. Therefore, we recommend carrying out further studies with in vitro tests and subsequent clinical tests to analyze its effectiveness in the treatment of SARS‑CoV‑2.

Enhanced Loading of Paclitaxel in Cationic Liposomes by Replacement of Oleoyl with Linoleoyl Lipid Tails with Benefits in Cancer Therapeutics from In Vitro Studies

Lipid-based carriers of the hydrophobic drug paclitaxel (PTX) are used in clinical trials as next-generation agents for cancer chemotherapy. Improving the loading capacity of these carriers requires enhanced PTX solubilization. We compared the solubility of PTX in cationic liposomes (CLs) with lipid tails containing one (oleoyl; C18:1 Δ9; DOTAP/DOPC) or two (linoleoyl; C18:2 Δ9; DLinTAP/DLinPC) cis double bonds with newly synthesized cationic DLinTAP (2,3-dilinoleoyloxypropyltrimethylammonium methylsufate). We used differential-interference-contrast microscopy to directly observe PTX crystal formation and generate kinetic phase diagrams representing the time-dependence of PTX solubility as a function of PTX content in the membrane. Replacing tails bearing one cis double bond (DO lipids) with those bearing two (DLin lipids) significantly increased PTX membrane solubility in CLs. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the membrane solubility limit which has been the focus of most previous fundamental studies and clinical trials) in DOTAP/DOPC CLs. The large increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX upon replacement of oleoyl by linoleoyl tails, rather than by the transition in membrane structure from lipid bilayers to inverse cylindrical micelles observed in small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against human prostate cancer (PC3) cells from measurements of the IC50 of PTX cytotoxicity was unaffected by changing the lipid tails, and toxicity of the CL carrier alone was negligible. Moreover, efficacy was approximately doubled against human melanoma (M21) cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. The findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading well over the typically used 3 mol% while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.