Fabrications, Classifications, and Environmental Impact of PCM-Incorporated Textiles: Current State and Future Outlook.

Phase change materials (PCMs) are an extraordinary family of compounds that can store and release thermal energy during phase changes. In recent years, the incorporation of PCMs into textiles has attracted considerable interest, since it represents a unique way to improve the comfort and usefulness of textiles. This article examines the advancements achieved in the preparation, classifications, and environmental effects of PCM-integrated textiles, along with a roadmap for the future. Progress of different PCM has been reported including its pros and cons. In addition, fabrications of the PCM on the apparel have been highlighted. Moreover, this Review analyzed the positive environmental impact of PCM-integrated textiles including improved insulation, extended product lifespan, and energy savings along with negative effects like higher energy consumption in the manufacturing process, added chemical additives tending to have a negative impact on the environment, less disposal features textiles and many more with recent references. Moreover, the future outlook also reports more research on nanoencapsulation, making it energy efficient, ensuring affordability, and more applications in smart PCM textiles. It seeks to stimulate additional research, encourage innovation, and contribute to the creation of high-performance, energy-efficient textiles by investigating the possibilities of PCM-enhanced textiles. The future of PCM in textiles is hopeful, with continuous research and technological advances resolving the aforementioned difficulties.

In vivo targeting of a tumor-antigen encoded DNA vaccine to dendritic cells in combination with tumor-selective chemotherapy eradicates established mouse melanoma.

Despite remarkable progress during the past decade, eradication of established tumors by targeted cancer therapy and cancer immunotherapy remains an uphill task. Herein, we report on a combination approach for eradicating established mouse melanoma. Our approach employs the use of tumor selective chemotherapy in combination with in vivo dendritic cell (DC) targeted DNA vaccination. Liposomes of a newly synthesized lipopeptide containing a previously reported tumor-targeting CGKRK-ligand covalently grafted in its polar head-group region were used for tumor selective delivery of cancer therapeutics. Liposomally co-loaded STAT3siRNA and WP1066 (a commercially available inhibitor of the JAK2/STAT3 pathway) were used as cancer therapeutics. In vivo targeting of a melanoma antigen (MART-1) encoded DNA vaccine (p-CMV-MART1) to dendritic cells was accomplished by complexing it with a previously reported mannose-receptor selective in vivo DC-targeting liposome. Liposomes of the CGKRK-lipopeptide containing encapsulated FITC-labeled siRNA, upon intravenous administration in B16F10 melanoma bearing mice, showed remarkably higher accumulation in tumors 24 h post i.v. treatment, compared to their degree of accumulation in other body tissues including the lungs, liver, kidneys, spleen and heart. Importantly, the findings in tumor growth inhibition studies revealed that only in vivo DC-targeted genetic immunization or only tumor-selective chemotherapy using the presently described systems failed to eradicate the established mouse melanoma. The presently described combination approach is expected to find future applications in combating various malignancies (with well-defined surface antigens).

(Pyridylamido)Hf(IV)-Catalyzed 1-Octene Polymerization Reaction Interwoven with the Structural Dynamics of the Ion-Pair-Active Species: Bridging from Microscopic Simulation to Chemical Kinetics with the Red Moon Method.

We performed the atomistic simulation of 1-octene polymerization reaction catalyzed by the ionic pair (IP) consisting of the cationic active species of (pyridylamido)Hf(IV) catalyst, HfCatPn+, and different counteranions (CAs), B(C6F5)4- and MeB(C6F5)3-, at different monomer concentrations. Using a hybrid Monte Carlo/molecular dynamics method, that is, the Red Moon (RM) method, the reaction progress measured by the "RM cycle" was transformed into effective real time using the time transformation theory. Then, the degree of polymerization was found to be consistent with that in the chemical kinetics, a macroscopic theory, and experimental ones. Remarkably, the current simulation has revealed the different dynamical features in the polymerization behavior originating from the CA. Namely, the HfCatPn+-B(C6F5)4- IP mainly forms an outer-sphere IP (OSIP) throughout the polymerization. The HfCatPn+-MeB(C6F5)3- IP, on the other hand, forms an inner-sphere IP (ISIP) in the initial stage of polymerization, and the ratio of ISIP steeply drops after the first monomer insertion because the IP interaction is reduced by the steric hindrance between the inserted monomers and the CA. In conclusion, we have shown that the microscopic IP dynamics interwoven with the polymerization reaction can be computationally observed in the real-time domain by using the RM method. Therefore, our current work demonstrates the promising potential of the RM method in studying catalytic olefin polymerization and complex chemical reaction systems.

Genome characterization, phylogenomic assessment and spatio-temporal dynamics study of highly mutated BA variants from India.

PURPOSE: The emergence of highly mutated and transmissible BA variants has caused an unprecedented surge in COVID-19 infections worldwide. Thorough analysis of its genome structure and phylogenomic evolutionary details will serve as scientific reference for future research. METHOD: Here, we have analyzed the BA variants from India using whole-genome sequencing, spike protein mutation study, spatio-temporal surveillance, phylogenomic assessment and epitope mapping. RESULTS: The predominance of BA.2/BA.2-like was observed in India during COVID-19 third wave. Genome analysis and mutation study highlighted the existence of 2128 amino acid changes within BA as compared to NC_045512.2. Presence of 23 unknown mutation sites (spanning region 61-831) were observed among the Indian BA variants as compared to the global BA strains. Unassigned probable Omicron showed the highest number of mutations (370) followed by BA.1 (104), BA.2.3 (56), and BA.2 (27). Presence of mutations 'Q493R â€‹+ â€‹Q498R â€‹+ â€‹N501Y', and 'K417 â€‹N â€‹+ â€‹E484A â€‹+ â€‹N501Y' remained exclusive to BA.2 as well as unassigned probable Omicron. The time-tree and phylogenomic network assessed the evolutionary relationship of the BA variants. Existence of 424 segregating sites and 113 parsimony informative sites within BA genomes were observed through haplotype network analysis. Epitope mapping depicted the presence of unique antigenic sites within the receptor binding domain of the BA variants that could be exploited for robust vaccine development. CONCLUSION: These findings provide important scientific insights about the nature, diversity, and evolution of Indian BA variants. The study further divulges in the avenues of therapeutic upgradation for better management and eventual eradication of COVID-19.

Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.

Locally advanced pancreatic tumours are highly resistant to conventional radiochemotherapy. Here we show that such resistance can be surmounted by an injectable depot of thermally responsive elastin-like polypeptide (ELP) conjugated with iodine-131 radionuclides (131I-ELP) when combined with systemically delivered nanoparticle albumin-bound paclitaxel. This combination therapy induced complete tumour regressions in diverse subcutaneous and orthotopic mouse models of locoregional pancreatic tumours. 131I-ELP brachytherapy was effective independently of the paclitaxel formulation and dose, but external beam radiotherapy (EBRT) only achieved tumour-growth inhibition when co-administered with nanoparticle paclitaxel. Histological analyses revealed that 131I-ELP brachytherapy led to changes in the expression of intercellular collagen and junctional proteins within the tumour microenvironment. These changes, which differed from those of EBRT-treated tumours, correlated with the improved delivery and accumulation of paclitaxel nanoparticles within the tumour. Our findings support the further translational development of 131I-ELP depots for the synergistic treatment of localized pancreatic cancer.

Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.

The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation state in the same nanoparticle system that would allow its optimal design. To address this lacuna, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enables covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by ∼45-fold, but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.

A Nanoparticle's Journey to the Tumor: Strategies to Overcome First-Pass Metabolism and Their Limitations.

Nanomedicines represent the cutting edge of today's cancer therapeutics. Seminal research decades ago has begun to pay dividends in the clinic, allowing for the delivery of cancer drugs with enhanced systemic circulation while also minimizing off-target toxicity. Despite the advantages of delivering cancer drugs using nanoparticles, micelles, or other nanostructures, only a small fraction of the injected dose reaches the tumor, creating a narrow therapeutic window for an otherwise potent drug. First-pass metabolism of nanoparticles by the reticuloendothelial system (RES) has been identified as a major culprit for the depletion of nanoparticles in circulation before they reach the tumor site. To overcome this, new strategies, materials, and functionalization with stealth polymers have been developed to improve nanoparticle circulation and uptake at the tumor site. This review summarizes the strategies undertaken to evade RES uptake of nanomedicines and improve the passive and active targeting of nanoparticle drugs to solid tumors. We also outline the limitations of current strategies and the future directions we believe will be explored to yield significant benefits to patients and make nanomedicine a promising treatment modality for cancer.

Novel Suberoylanilide Hydroxamic Acid Analogs Inhibit Angiogenesis and Induce Apoptosis in Breast Cancer Cells.

BACKGROUND: Histone deacetylases (HDACs) are the enzymes that catalyze the removal of the acetyl group from lysine residues and regulate several biological processes. Suberoylanilide hydroxamic acid (SAHA) is a notable HDAC inhibitor that exhibited remarkable anti-proliferative efficiency by alleviating gene regulation against solid and hematologic cancers. AIM: The aim of this study was to develop new chemotherapeutic agents for breast cancer treatment, therefore, a novel series of Suberoylanilide hydroxamic acid (SAHA) analogs were investigated as anticancer agents. METHODS: We designed and synthesized a novel series of analogs derived from SAHA by substituting alkyl, alkoxy, halo, and benzyl groups at different positions of the phenyl ring. The newly synthesized analogs were assessed for their cytotoxic potential against four human cancer cell lines in comparison with healthy cell lines, using several biological assays. RESULTS: SAHA analogs displayed significant cytotoxic potential with IC50 values ranging from 1.6 to 19.2 µM in various tumor cell lines. Among these analogs, 2d (containing 3-chloro, 4-floro substitutions on phenyl moiety), 2h (containing 3,4-di chloro substitutions on phenyl moiety), and 2j (containing 4-chloro, 3-methyl substitutions on phenyl moiety) showed significant cytotoxic potential with IC50 values ranging from 1.6 to 1.8 µM in MCF-7 (breast carcinoma) cell line. More importantly, these analogs were found to be non-toxic towards healthy primary human hepatocytes (PHH) and mouse fibroblast cells (NIH3T3), which represent their tumor selectivity. These analogs were further analyzed for their effect on cell migration, BrdU incorporation, Annexin V-FITC and cell cycle arrest (Sub-G1 phase). Remarkably, analogs 2d, 2h, and 2j displayed significant HDAC inhibition than the parent SAHA molecule. Further studies also confirmed that these SAHA analogs are efficient in inducing apoptosis, as they regulated the expression of several proteins involved in mitochondrial or intrinsic apoptosis pathways. Findings in the Chick Chorioallantoic Membrane (CAM) assay studies revealed anti-angiogenic properties of the currently described SAHA analogs. CONCLUSION: From anti-proliferative study results, it is clearly evident that 3,4-substitution at the SAHA phenyl ring improves the anti-proliferative activity of SAHA. Based on these findings, we presume that the synthesized novel SAHA analogs could be potential therapeutic agents in treating breast cancer.

Genetically encoded elastin-like polypeptide nanoparticles for drug delivery.

Small molecule drugs suffer from poor in vivo half-life, rapid degradation, and systemic off-target toxicity. To address these issues, researchers have developed nanoparticles that significantly enhance the delivery of many drugs while reducing their toxicity and improving targeting to specific organs. Recombinantly synthesized biomaterials such as elastin-like polypeptides (ELPs) have unique attributes that greatly facilitate the rational design of nanoparticles for drug delivery. These attributes include biocompatibility, precise control over amino acid sequence design, and stimuli-responsive self-assembly into nanostructures that can be loaded with a range of drugs to enhance their pharmacokinetics and pharmacodynamics, significantly improving their therapeutic efficacy over the free drugs. This review summarizes recent developments in genetically encoded, self-assembling ELP nanoparticles and their applications for drug delivery.

Genomic Surveillance and Phylodynamic Analyses Reveal the Emergence of Novel Mutations and Co-mutation Patterns Within SARS-CoV-2 Variants Prevalent in India.

Identification of the genomic diversity and the phylodynamic profiles of prevalent variants is critical to understand the evolution and spread of SARS-CoV-2 variants. We performed whole-genome sequencing of 54 SARS-CoV-2 variants collected from COVID-19 patients in Kolkata, West Bengal during August-October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad that are available in the GISAID database. We estimated the clade dynamics of the Indian variants and compared the clade-specific mutations and the co-mutation patterns across states and union territories of India over the time course. Frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating the emergence of newer mutations in the viral population prevailing in the country. Furthermore, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested in Indian patients.

Controlling One-Electron vs Two-Electron Pathways in the Multi-Electron Redox Cycle of Nickel Diethyldithiocarbamate.

The unique redox cycle of NiII(dtc)2, where dtc- is N,N-diethyldithiocarbamate, in acetonitrile displays 2e- redox chemistry upon oxidation from NiII(dtc)2 → [NiIV(dtc)3]+ but 1e- redox chemistry upon reduction from [NiIV(dtc)3]+ → NiIII(dtc)3 → NiII(dtc)2. The underlying reasons for this cycle lie in the structural changes that occur between four-coordinate NiII(dtc)2 and six-coordinate [NiIV(dtc)3]+. Cyclic voltammetry (CV) experiments show that these 1e- and 2e- pathways can be controlled by the addition of pyridine-based ligands (L) to the electrolyte solution. Specifically, the addition of these ligands resulted in a 1e- ligand-coupled electron transfer (LCET) redox wave, which produced a mixture of pyridine-bound Ni(III) complexes, [NiIII(dtc)2(L)]+, and [NiIII(dtc)2(L)2]+. Although the complexes could not be isolated, electron paramagnetic resonance (EPR) measurements using a chemical oxidant in the presence of 4-methoxypyridine confirmed the formation of trans-[NiIII(dtc)2(L)2]+. Density functional theory calculations were also used to support the formation of pyridine coordinated Ni(III) complexes through structural optimization and calculation of EPR parameters. The reversibility of the LCET process was found to be dependent on both the basicity of the pyridine ligand and the scan rate of the CV experiment. For strongly basic pyridines (e.g., 4-methoxypyridine) and/or fast scan rates, high reversibility was achieved, allowing [NiIII(dtc)2(L)x]+ to be reduced directly back to NiII(dtc)2 + xL. For weakly basic pyridines (e.g., 3-bromopyridine) and/or slow scan rates, [NiIII(dtc)2(L)x]+ decayed irreversibly to form [NiIV(dtc)3]+. Detailed kinetics studies using CV reveal that [NiIII(dtc)2(L)]+ and [NiIII(dtc)2(L)2]+ decay by parallel pathways due to a small equilibrium between the two species. The rate constants for ligand dissociation ([NiIII(dtc)2(L)2]+ → [NiIII(dtc)2(L)]+ + L) along with decomposition of [NiIII(dtc)2(L)]+ and [NiIII(dtc)2(L)2]+ species were found to increase with the electron-withdrawing character of the pyridine ligand, indicating pyridine dissociation is likely the rate-limiting step for decomposition of these complexes. These studies establish a general trend for kinetically trapping 1e- intermediates along a 2e- oxidation path.

Dissipation behaviour and risk assessment of fipronil and its metabolites in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS.

Fipronil -a broad spectrum phenylpyrazole insecticide has high level of toxicity towards environment. Therefore, an easy and reliable analytical method was developed for residue estimation of fipronil to ensure food and environmental safety. A modified QuEChERS technique was followed for estimation of fipronil (5% SC) in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS. The initial residues (0.168-0.794 µg g-1) of total fipronil i.e., sum of fipronil and its metabolites (viz., desulfinyl and sulfone) in leaf and soil were dissipated following first order kinetics. About 92-96% of fipronil residues were degraded after 15 days with half-life of 3.4-4.1 days and pre-harvest interval of 19.4-25.7 days in plant. Residues were below level of quantification (<0.005 µg g-1) in plant and soil at harvest. The fipronil residues in rice grain present low dietary risk (RQd < 1) to human health. However, high risk (RQd > 1) was predicted for cattle health due to fipronil residues in paddy leaf up to 10 days. The residual level in soil was also at highrisk (RQs > 1) for soil ecological health.

Towards developing a criterion to characterize non-covalent bonds: a quantum mechanical study.

Chemical bonds are central to chemistry, biology, and allied fields, but still, the criterion to characterize an interaction as a non-covalent bond has not been studied rigorously. Therefore, in this study, we have attempted to characterize the non-covalent bonds by considering a total of 85 model systems depicting different chemical bonds comprising 43 non-covalent and 42 other bonds such as covalent, ionic, and coordinate bonds. The characterization has been done based on interaction energy, energy decomposition analysis (EDA), the NCI plot, and the analysis of topological properties of electron density. The interaction energy values, energy decomposition analysis, and NCI plot give insights into the full understanding of bond strength and its nature, but they fail to distinctively characterize the interaction as a non-covalent bond. Herein, a special criterion has been developed based on the topological parameters to characterize an interaction as a non-covalent bond. Topological parameters illustrate that the values of both ∇2ρ and H(r) are positive with a value of ρ < 0.03 a.u. and [-G(r)/V(r)] ≥ 1.00 for the non-covalent bonds. The value of ρ increases up to 0.06 a.u. with a positive value of ∇2ρ and a negative value of H(r) if the non-covalent bond is partially covalent in nature. The analysis of G(r) suggests that it dominates the H(r) of non-covalent bonds with greater than 50% contribution, whereas the contribution of G(r) varies between 35 and 50% in the case of bonds which are partially covalent in nature. The criterion based on topological parameters is likely to be very helpful to comprehend and ascertain the non-covalent bonds in the chemical as well as complex biological systems.

Atomistic Simulation of the Polymerization Reaction by a (Pyridylamido)hafnium(IV) Catalyst: Counteranion Influence on the Reaction Rate and the Living Character of the Catalytic System.

Atomistic simulation of the 1-octene polymerization reaction by a (pyridylamido)Hf(IV) catalyst was conducted on the basis of Red Moon (RM) methodology, focusing on the effect of the counteranions (CAs), MeB(C6F5)3-, and B(C6F5)4-, on the catalyst activity and chain termination reaction. We show that RM simulation reasonably reproduces the faster reaction rate with B(C6F5)4- than with MeB(C6F5)3-. Notably, the initiation of the polymerization reaction with MeB(C6F5)3- is comparatively slow due to the difficulty of the first insertion. Then, we investigated the free energy map of the ion pair (IP) structures consisting of each CA and the cationic (pyridylamido)Hf(IV) catalyst with the growing polymer chain (HfCatPn+), which determines the polymerization reaction rates, and found that HfCatPn+-MeB(C6F5)3- can keep forming "inner-sphere" IPs even after the polymer chain becomes sufficiently bulky, while HfCatPn+-B(C6F5)4- forms mostly "outer-sphere" IPs. Finally, we further tried to elucidate the origin of the broader molecular weight distribution (MWD) of the polymer experimentally produced with B(C6F5)4- than that with MeB(C6F5)3-. Then, through the trajectory analysis of the RM simulations, it was revealed that the chain termination reaction would be more sensitive to the IP structures than the monomer insertion reaction because the former involves a more constrained structure than the latter, which is likely to be a possible origin of the MWDs dependent on the CAs.

Synthesis, characterization, and electrocatalytic activity of bis(pyridylimino)isoindoline Cu(II) and Ni(II) complexes.

Two NNN pincer complexes of Cu(ii) and Ni(ii) with BPIMe- [BPIMe- = 1,3-bis((6-methylpyridin-2-yl)imino)isoindolin-2-ide] have been prepared and characterized structurally, spectroscopically, and electrochemically. The single crystal structures of the two complexes confirmed their distorted trigonal bipyramidal geometry attained by three equatorial N-atoms from the ligand and two axially positioned water molecules to give [Cu(BPIMe)(H2O)2]ClO4 and [Ni(BPIMe)(H2O)2]ClO4. Electrochemical studies of Cu(ii) and Ni(ii) complexes have been performed in acetonitrile to identify metal-based and ligand-based redox activity. When subjected to a saturated CO2 atmosphere, both complexes displayed catalytic activity for the reduction of CO2 with the Cu(ii) complex displaying higher activity than the Ni(ii) analogue. However, both complexes were shown to decompose into catalytically active heterogeneous materials on the electrode surface over extended reductive electrolysis periods. Surface analysis of these materials using energy dispersive spectroscopy as well as their physical appearance suggests the reductive deposition of copper and nickel metal on the electrode surface. Electrocatalysis and decomposition are proposed to be triggered by ligand reduction, where complex stability is believed to be tied to fluxional ligand coordination in the reduced state.

Theoretically predicting the feasibility of highly-fluorinated ethers as promising diluents for non-flammable concentrated electrolytes.

The practical application of nonflammable highly salt-concentrated (HC) electrolyte is strongly desired for safe Li-ion batteries. Not only experimentalists but also theoreticians are extensively focusing on the dilution approach to address the limitations of HC electrolyte such as low ionic conductivity and high viscosity. This study suggests promising highly-fluorinated ethers to dilute the HC electrolyte based on non-flammable trimethyl phosphate (TMP) solvent. According to the quantum mechanical and molecular dynamics calculations, the fluorinated ether diluents showed a miscibility behavior in HC TMP-based electrolyte. While such miscibility behavior of the diluent with TMP solvent has been significantly enhanced by increasing its degree of fluorination, i.e., the "fluorous effect", it is remarkable that the self-diffusion constant of Li+ and the ionic conductivity should be significantly improved by dilution with bis(1,1,2,2-tetrafluoro ethyl) ether (B2E) and bis(pentafluoro ethyl) ether (BPE) compared to other common hydrofluoroether diluents. In addition, the fluorinated-ether diluents have high ability to form a localized-concentrated electrolyte in HC TMP-based solution, leading to high expectation for the formation of a stable and a compact inorganic SEI film.

Recent trends in protein and peptide-based biomaterials for advanced drug delivery.

Engineering protein and peptide-based materials for drug delivery applications has gained momentum due to their biochemical and biophysical properties over synthetic materials, including biocompatibility, ease of synthesis and purification, tunability, scalability, and lack of toxicity. These biomolecules have been used to develop a host of drug delivery platforms, such as peptide- and protein-drug conjugates, injectable particles, and drug depots to deliver small molecule drugs, therapeutic proteins, and nucleic acids. In this review, we discuss progress in engineering the architecture and biological functions of peptide-based biomaterials -naturally derived, chemically synthesized and recombinant- with a focus on the molecular features that modulate their structure-function relationships for drug delivery.

Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma.

PURPOSE: Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations. EXPERIMENTAL DESIGN: New drug formulations can be tested in animal models of sarcomas where the therapeutic response of different formulations can be compared using mice with identical tumor-initiating mutations. Here, using Cre/loxP and CRISPR/Cas9 techniques, we generated two distinct mouse models of Pten-deleted soft-tissue sarcoma: malignant peripheral nerve sheath tumor (MPNST) and undifferentiated pleomorphic sarcoma (UPS). We used these models to test the efficacy of chimeric polypeptide doxorubicin (CP-Dox), a nanoscale micelle formulation, in comparison with free doxorubicin. RESULTS: The CP-Dox formulation was superior to free doxorubicin in MPNST models. However, in UPS tumors, CP-Dox did not improve survival in comparison with free doxorubicin. While CP-Dox treatment resulted in elevated intratumoral doxorubicin concentrations in MPNSTs, this increase was absent in UPS tumors. In addition, elevation of CD8+ T cells was observed exclusively in CP-Dox-treated MPNSTs, although these cells were not required for full efficacy of the CP nanoparticle-based chemotherapy. CONCLUSIONS: These results have important implications for treating sarcomas with nanoparticle-encapsulated chemotherapy by highlighting the tumor subtype-dependent nature of therapeutic response.

Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma.

Combating brain tumors (glioblastoma multiforme or GBM) is a formidable challenge because of the existence of blood-brain barrier (BBB), a tight cellular junction that separates the central nervous system (CNS) and systemic circulation. Such a selectively permeable barrier prevents the entry of therapeutic molecules from blood circulation to brain parenchyma. Towards enhancing the efficacy of brain tumor-selective drug delivery without perturbing the BBB integrity, nanometric drug carriers are increasingly becoming an efficient therapeutic modality in preclinical studies. Psychostimulant drugs such as amphetamine and methylated amphetamine (METH) are known to penetrate the BBB. Still, little effort has been made to exploit them in nano-drug delivery, largely due to their toxicities. Herein, for the first time, we design, synthesize, and formulate three different ß-amphetaminylated cationic lipid nanoparticles. We show that the ß-amphetaminylated cationic lipid nanoparticles are nontoxic and can cross the BBB presumably through active transcytosis. The BBB penetrating ability also depends on the hydrophilic-hydrophobic balance of the lipids, with hexadecyl lipid (16-BACL) nanoparticle showing maximum accumulation in the brain. The lipid nanoparticle of 16-BACL can simultaneously encapsulate paclitaxel and PDL1-siRNA. The dual drug-loaded lipid nanoparticles showed apoptosis driven cellular cytotoxicity against GL261 cells and improved the overall survivability of orthotopic glioblastoma bearing mice compared to their non-targeting counterpart. The present work describes a new class of BBB-crossing lipid nanoparticles and delineates their therapeutic promise against glioblastoma.