pH-responsive Polymer Research Articles

PH-Responsive Polymer as a New Stable Solid Electrolyte Interphase for Water-in-Salt Battery

pH-Responsive Polymer as a New Stable Solid Electrolyte Interphase for Water-in-Salt Battery

Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Smart Accumulating Dual-Targeting Lipid Envelopes Equipping Oncolytic Adenovirus for Enhancing Cancer Gene Therapeutic Efficacy.

Systemic delivery of oncolytic adenovirus (oAd) for cancer gene therapy must overcome several limitations such as rapid clearance from the blood, nonspecific accumulation in the liver, and insufficient delivery to the tumor tissues. In the present report, a tumor microenvironment-triggered artificial lipid envelope composed of a pH-responsive sulfamethazine-based polymer (PUSSM)-conjugated phospholipid (DOPE-HZ-PUSSM) and another lipid decorated with epidermal growth factor receptor (EGFR) targeting peptide (GE11) (GE11-DOPE) was utilized to encapsulate replication-incompetent Ad (dAd) or oAd coexpressing short-hairpin RNA (shRNA) against Wnt5 (shWnt5) and decorin (dAd/LP-GE-PS or oAd/LP-GE-PS, respectively). In vitro studies demonstrated that dAd/LP-GE-PS transduced breast cancer cells in a pH-responsive and EGFR-specific manner, showing a higher level of transduction than naked Ad under a mildly acidic pH of 6.0 in EGFR-positive cell lines. In vivo biodistribution analyses revealed that systemic administration of oAd/LP-GE-PS leads to a significantly higher level of intratumoral virion accumulation compared to naked oAd, oAd encapsulated in a liposome without PUSSM or EGFR targeting peptide moiety (oAd/LP), or oAd encapsulated in a liposome with EGFR targeting peptide alone (oAd/LP-GE) in an EGFR overexpressing MDA-MB-468 breast tumor xenograft model, showing that both pH sensitivity and EGFR targeting ability were integral to effective systemic delivery of oAd. Further, systemic administration of all liposomal oAd formulations (oAd/LP, oAd/LP-GE, and oAd/LP-GE-PS) showed significantly attenuated hepatic accumulation of the virus compared to naked oAd. Collectively, our findings demonstrated that pH-sensitive and EGFR-targeted liposomal systemic delivery of oAd can be a promising strategy to address the conventional limitations of oAd to effectively treat EGFR-positive cancer in a safe manner.

Ethoxy Acetalated Dextran-Based Biomaterials for Therapeutic Applications.

A novel class of pH-responsive polymers, acetalated dextran, has emerged in the field of biomaterials. These versatile materials are derived from dextran through a simple acetalation reaction, allowing for the creation of polymers with a tunable release profile which allows the controlled release of encapsulated therapeutics in response to acidic environments. Despite their recent introduction, acetalated dextran has rapidly garnered significant interest due to its potential for various therapeutic applications. This review delves specifically into the recent advancements of ethoxy acetalated dextran or Ace-DEX, a particular acetalated dextran with a distinct advantage: its degradation products (acetone and ethanol) are less toxic compared to other variants that produce methanol. The focus of this review is the diverse range of biomedical applications currently being explored for Ace-DEX-based scaffolds. Finally, this review concludes by addressing the existing challenges associated with Ace-DEX and outlining potential future research directions within this promising field.

Development and Analysis of Colon-Specific, pH-Responsive Polymer Delivery of Irinotecan Hydrochloride Tablets for Colon Cancer Treatment.

For the formulation of enteric-coated tablets containing irinotecan hydrochloride, this thesis focuses on HPMC and ethylcellulose, both of which are pH- and oxidation-resistant polymers. The integrated polymer-drug tablet mixture was coated with 15% of eudragit S100 and L100, which is a methacrylic acid copolymers, that’s soluble at pH 7. Both the physical characteristics with the invitro release kinetics pattern of the enteric-coated tablets were characterized. In the invitro release study, different pH environments were used, comparable to the gastrointestinal tract (GIT): 0.1 N HCl solution for two hours, pH 6.8 phosphate buffer for three hours, and pH 7.4 phosphate buffer for six hours. Using this device, you can simulate the pH level of the mouth, the digestive tract, and the urinary tract. As a result of consistent release studies, formulation F7 released 88.2% of the drug after 12 hours. Models such as Higuchi, Korsmeyer-Peppas, and zero-order reactions were used to analyze the GIT. This directed the development of a sustained delivery pattern that may be perfect for colonic IRT administration in the eventual treatment of colon cancer. Among the nine formulations, F7 formulated with EC and HPMC extended best sustained release pattern of drug, hence it is suitable for treating colon cancer.

Realizing the Rapid Release of Drag Reducers via pH-Induced Oil Phase Transition of Inverse Emulsion.

As a key component of slickwater fracturing fluids, emulsion drag reducers play a vital role. The dissolving capacity of traditional emulsion drag reducers is improved by adding hydrophilic surfactants, which leads to poor stability of the emulsion drag reducer. In order to eliminate the contradiction between stability and release of the emulsion drag reducer, here, pH-responsive polymer emulsion was fabricated using the switching solvent (HA) and white oil as the continuous phase. Monomer emulsions exhibit obvious pH-responsive behavior. This is because the deprotonation of HA by pH stimulation leads to a change in the oil-water ratio of the emulsion, thereby facilitating the demulsification of emulsion. The remarkable stability of the monomer emulsion benefits the preparation of inverse emulsion polymers (P(AM-AA-AMPS)). The obtained P(AM-AA-AMPS) polymer emulsion features remarkable stability even after 15 days of storage. Importantly, the P(AM-AA-AMPS) polymer was released from the emulsion efficiently by pH stimulation instead of introducing an extra hydrophilic surfactant, which confirmed the improvement of polymer release by pH stimulation. The viscosity of the P(AM-AA-AMPS) polymer aqueous solution reaches a maximum value of 96 mPa s within 80 s at a pH value of 9.2. The release efficiency of P(AA-AM-AMPS) polymer emulsion is increased by 33% in comparison with that of traditional polymer emulsion (2 min). The P(AM-AA-AMPS) emulsion demonstrated remarkable drag-reduction performance by achieving a drag-reduction rate of 73% at a concentration of 0.05 wt %. P(AM-AA-AMPS) polymer emulsion with pH responsiveness eliminates the contradiction between the stability and release of emulsion drag reducers. Research based on pH-responsive P(AM-AA-AMPS) polymer emulsion provides other ideas for the development of quickly dissolving and long-term storage drag reducers, which is helpful for the development of low-permeability oil and gas resources.

Fluorescent, pH, and UCST Responsive Polymer Nanomaterials for Treatment of Recurrent Miscarriage.

Recurrent miscarriage (RM), defined as three or more consecutive spontaneous miscarriages, affects many women of childbearing age. The pathological basis of RM is an imbalance in apoptosis, with the MDM2-p53 pathway playing a crucial role. In this study, we synthesized poly(6-acetoxyl-ε-caprolactone)-graft-(4-amino-benzimidazole) (PCCL-4-ABI) by modifying poly(6-acetoxyl-ε-caprolactone) (PCCL) with 4-amino-benzimidazole (4-ABI). The introduction of carboxyl and 4-ABI groups endowed the PCL backbone with fluorescence, pH responsiveness, and UCST responsiveness. The temperature-dependent release behavior of compound 1-loaded PCCL-4-ABI nanofluorescent materials was attributed to UCST transition. We successfully developed a novel nanofluorescent polymer drug delivery platform, PCCL-4-ABI@1, and evaluated its regulatory effects on p53 and MDM2 in trophoblast cells (HTR-8/SVneo). The results showed that the system loaded with low molecular weight heparin increased MDM2 and decreased p53 expression in a dose-dependent manner, thereby inhibiting trophoblast cell apoptosis. This study developed a biodegradable poly(ε-caprolactone) with UCST behavior, significant for the advancement of thermoresponsive fluorescent nanoparticle systems.

Electrical and fluorescence in situ monitoring of tumor microenvironment-based pH-responsive polymer dot coated surface

A boronate-ester structure forming a pH-responsive polymer dot (Plu-PD) coated biosensor between carbonized-sp2 rich dopamine-alginate [PD(Alg)] and boronic acid-grafted Pluronic (BA-Pluronic) was developed for the electrochemical and fluorescence detection of cancer cells. The reduced fluorescence (FL) resulting from fluorescence resonance energy transfer (FRET) mediated by π-π interactions within Plu-PD was successfully reinvigorated through the specific cleavage of the boronate-ester bond, triggered by the acidic conditions prevailing in the cancer microenvironment. The anomalous variations in extracellular pH levels observed in cancer (pH ∼6.8), as opposed to the normal cellular pH range of approximately 7.4, serve as robust indicators for discerning cancer cells from their healthy counterparts. Moreover, the Plu-PD coated surface demonstrated remarkable adaptability in modulating its surface structure, concurrently exhibiting tunable electroconductivity under reduced pH conditions, thereby imparting selective responsiveness to cancer cells. The pH-modulated conductivity change was validated by a reduction in resistance from 211 ± 9.7 kΩ at pH 7.4 to 73.9 ± 9.4 kΩ and 61.5 ± 11.5 kΩ at pH 6.8 and 6.0, respectively. The controllable electrochemical characteristics were corroborated through in vitro treatment of cancer cells (HeLa, B16F10, and SNU-C2A) via LED experiments and wireless output analysis. In contrast, identical treatments yielded a limited response in normal cell line (CHO–K1). Notably, the Plu-PD coated surface can be seamlessly integrated with a wireless system to facilitate real-time monitoring of the sensing performance in the presence of cancer and normal cells, enabling rapid and accurate cancer diagnosis using a smartphone.

Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.

Nanosensor-Enabled Detection and Identification of Intracellular Bacterial Infections in Macrophages.

Opportunistic bacterial pathogens can evade the immune response by residing and reproducing within host immune cells, including macrophages. These intracellular infections provide reservoirs for pathogens that enhance the progression of infections and inhibit therapeutic strategies. Current sensing strategies for intracellular infections generally use immunosensing of specific biomarkers on the cell surface or polymerase chain reaction (PCR) of the corresponding nucleic acids, making detection difficult, time-consuming, and challenging to generalize. Intracellular infections can induce changes in macrophage glycosylation, providing a potential strategy for signature-based detection of intracellular infections. We report here the detection of bacterial infection in macrophages using a boronic acid (BA)-based pH-responsive polymer sensor array engineered to distinguish mammalian cell phenotypes by their cell surface glycosylation signatures. The sensor was able to discriminate between different infecting bacteria in minutes, providing a promising tool for diagnostic and screening applications.

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.Graphical

Antimicrobial silver loading onto reused high-density polyethylene matrices grafted with poly(4-vinylpyridine)

High-density polyethylene HDPE is a highly polluting plastic, and its reuse, reprocessing and modification are subjects of current research to mitigate environmental pollution. In recent times, it has been modified for specialized purposes as a harmless and resistant polymer. The present work details the modification of HDPE (obtained from Bonafont, Coke, and Gatorade caps) with the monomer 4-vinylpyridine (4VP) via radiation-induced grafting copolymerization initiated by gamma rays from a Co-60 source and with the subsequent Ag(I) loading using the reagent AgNO3 in aqueous medium. Poly(4VP) is widely used to retain metals and manufacture pH-responsive polymers, while Ag(I) is a recognized bactericide harmless to humans at therapeutic concentrations; therefore, both poly4VP and Ag(I) can work in a synergistic system against pathologic bacteria as is here proposed. We advance a favorable antimicrobial activity of the Ag-loaded graft copolymers evaluated in vitro with Kirby-Bauer tests against Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, FTIR-ATR, TGA, contact angle, swelling, and pH response were carried out to complete the characterization.

Mesoporous Fe3O4/SiO2/poly(2-carboxyethyl acrylate) composite polymer particles for pH-responsive loading and targeted release of bioactive molecules.

pH-responsive polymer microspheres undergoing reversible changes in their surface properties have been proved useful for drug delivery to targeted sites. This paper is aimed at preparing pH-responsive polymer-modified magnetic mesoporous SiO2 particles. First, mesoporous magnetic (Fe3O4) core-particles are prepared using a one-pot solvothermal method. Then, magnetic Fe3O4 particles are covered with a C[double bond, length as m-dash]C functional mesoporous SiO2 layer before seeded emulsion polymerization of 2-carboxyethyl acrylate (2-CEA). The composite polymer particles are named Fe3O4/SiO2/P(2-CEA). The average diameters of the Fe3O4 core and Fe3O4/SiO2/P(2-CEA) composite polymer particles are 414 and 595 nm, respectively. The mesoporous (pore diameter = 3.41 nm) structure of Fe3O4/SiO2/P(2-CEA) composite polymer particles is confirmed from Brunauer-Emmett-Teller (BET) surface analysis. The synthesized Fe3O4/SiO2/P(2-CEA) composite polymer exhibited pH-dependent changes in volume and surface charge density due to deprotonation of the carboxyl group under alkaline pH conditions. The change in the surface properties of Fe3O4/SiO2/P(2-CEA) composite polymer particles following pH change is confirmed from the pH-dependent sorption of cationic methylene blue (MB) and anionic methyl orange (MO) dye molecules. The opening of the pH-responsive P(2-CEA) gate valve at pH 10.0 allowed the release of loaded vancomycin up to 99% after 165 min and p-acetamido phenol (p-AP) up to 46% after 225 min. Comparatively, the amount of release is lower at pH 8.0 but still suitable for drug delivery applications. These results suggested that the mesoporous Fe3O4/SiO2 composite seed acted as a microcapsule, while P(2-CEA) functioned as a gate valve across the porous channel. The prepared composite polymer can therefore be useful for treating intestine/colon cancer, where the pH is comparatively alkaline.

Realizing the Efficient Dissolution of Drag Reducer upon pH-Induced Demulsification of Inverse Polymer Emulsion.

The increasing exploitation of fossil resources needs to shift people's attention to developing unconventional reservoir resources. Polyacrylamide-based emulsion drag reducers can effectively reduce the turbulence of fracturing fluid and improve oil recovery, but their release effect is poor, which limits their practical application. Here, we constructed a pH-responsive inverse polymer emulsion of poly(acrylamide-2-acrylamido-2-methylpropanesulfonic acid). Interestingly, HOA/Tween 80 exhibits remarkable pH-responsive behavior, which enables the monomer emulsion to change the type of emulsion under pH stimulation. Our results propose that the P(AM-AMPS) polymer emulsion is eluted with the same aqueous phase as the W/O P(AM-AMPS) polymer emulsion, thereby achieving the effect of drag reduction. P(AM-AMPS) can be rapidly released from the inverse polymer emulsion within 70 s upon pH stimulation, the drag reduction rate of which was 60.4%. Obviously, the inverse polymer emulsion prepared by a pH-responsive surfactant not only has good stability but also can achieve rapid release of the polymer upon pH stimulation, which supplies an interesting indication to explain why a balance exists between the stability of the emulsion and release of P(AM-AMPS).

PH-Sensitive Polymers with their Important Applications (A Review)

Abstract:: Materials that modify their chemical or physical characteristics in reaction to diverse stimuli, such as moisture, heat, water, or pH, are commonly known as smart materials or stimuli-responsive polymers. Typical applications for these polymers include catalysis, finishing, and coating processes. Tissue engineering, drug delivery, and gene transportation are additional applications that have emerged in the past two decades. As a result, their potential use extends to a wider range of applications, encompassing chemical processes, drug delivery, body-site targeting, separation, membrane activity, sensing and actuation, and agriculture. Recently, pH-responsive polymers have garnered considerable interest for implementation in membrane and 4D printing. The current review work encompasses previously published research through 2022, with a particular focus on the critical application of pH-sensitive polymers.

Near-Infrared Light-Triggered NO Nanogenerator for Gas-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy to Eliminate Biofilms.

Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on the r 1 of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM−1s−1 at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effect in vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

Nanozyme-catalyzed oxygen self-supplying mitochondria-targeting nanoplatform for precise photodynamic therapy

Local hypoxia in tumors poses significant challenges to the effectiveness of oxygen-dependent photodynamic therapy (PDT). Herein, a versatile mitochondrial targeting and pH-responsive nanozyme platform (noted as Mito CPs-p) is developed for solving local hypoxia in tumors and enhancing the PDT efficiency. Mito CPs-p, which consists of carbon-dot-supported atomically dispersed platinum (CPs) with further surface modifications of triphenylphosphine (PPh3) and pH-responsive porphyrin polymers. The PDT of Mito CPs-p was activated in acidic tumor microenvironment and exposed platinum for catalyzing endogenous H2O2 decomposition to produce O2 at tumor sites, due to the hydrophobic-hydrophilic transition of pH-responsive porphyrin-containing polymers in Mito CPs-p from hydrophobic to hydrophilic, which can markedly enhance PDT efficiency. Besides, the rational integration of mitochondria-targeting will improve the bioavailability of reactive oxygen species and further strengthen the PDT efficiency. In vitro results indicated that Mito CPs-p has exhibited excellent mitochondrial targeting capability and the ROS yield of Mito CPs-p was dramatically amplified. In vivo data further revealed that the Mito CPs-p displayed superb therapeutic efficacy. Hence, the Mito CPs-p provides new insights for efficient PDT in hypoxia solid tumors.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 μM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6.37), which preferentially selected cancerous cells with a favorable dose reduction (dose reduction index (DRI) of HCFU was 4.09). Moreover, the growth of CRC in tumor-bearing mice was effectively suppressed, with tumor suppression rates up to 94.74%, and a combination index (CI) value of less than one (CI = 0.41 for CT26 cell lines), indicating a significant synergistic therapeutic effect. Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-β levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC.