pH-responsive Polymer Research Articles

Research on a self-thickening and pH-responsive acidification polymer

Research on a self-thickening and pH-responsive acidification polymer

Photoconjugation of temperature- and pH-responsive polymer with silica nanoparticles for separation and enrichment of bacteria

A new photoconjugation approach was developed to prepare nanoparticle-supported boronic acid polymer for effective separation and enrichment of bacteria. The photo-activated polymer immobilization was demonstrated by coupling an azide-modified copolymer of N-isopropylacrylamide and glycidyl methacrylate to a perfluorophenyl azide-modified silica surface. The thermoresponsive polymer was synthesized using reversible addition fragmentation chain transfer polymerization followed by conversion of the pendant epoxides into azide groups. The perfluorophenyl azide-modified silica nanoparticles were synthesized by an amidation reaction between amino-functionalized silica and pentafluorobenzoyl chloride, and a subsequent treatment with sodium azide. Bacteria-capturing boronic acid was conjugated to the silica-supported polymer chains via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. The particle size, morphology and organic content of the composite nanoparticles were characterized systematically. The capability of the nanocomposite to bind Gram-positive and Gram-negative bacteria was investigated. The nanocomposite exhibited high binding capacities for E. coli (13.4 × 107 CFU/mg) and S. epidermidis (7.66 × 107 CFU/mg) in phosphate buffered saline. The new photoconjugation strategy enables fast and straightforward grafting of functional polymers on surface, which opens many new opportunities for designing functional materials for bioseparation and biosensing.

Colon targeted delivery of niclosamide from β-cyclodextrin inclusion complex incorporated electrospun Eudragit® L100 nanofibers

Electrospun nanofibers incorporated with inclusion complex (IC) of niclosamide (NIC) and hydroxypropyl-beta-cyclodextrin (HPβCD) (NIC-HPβCD-IC) was produced from pH-responsive polymer (Eudragit® L100, EUD), which disintegrates at pH values higher than 6, (EUD-NIC-HPβCD-IC-NF) for targeted delivery of NIC to the colon. Pristine EUD nanofibers (EUD-NF), only NIC loaded (EUD-NIC-NF) and physical mixture of NIC and HPβCD loaded EUD nanofibers (EUD-NIC-HPβCD-NF) were also produced as reference. SEM images revealed the bead-free and uniform morphology of nanofibers. XRD, TGA, and DSC were also performed for both NIC-HPβCD-IC and electrospun nanofibers and it was seen that there are some NIC molecules, which cannot make IC. Dissolution studies were carried out for 240 min at pH 1.2 and pH 7 simulating stomach and colon, respectively. EUD-NIC-NF released almost 53 % of NIC in 120 min, whereas EUD-NIC-HPβCD-NF (15 %) and EUD-NIC-HPβCD-IC-NF (8 %) released at most 15 % of NIC in 120 min. Then, remained NIC in the nanofibers released into the colon for the next 120 min. The slight difference in the release of NIC into stomach from EUD-NIC-HPβCD-NF and EUD-NIC-HPβCD-IC-NF might be due to the uncomplexed NIC molecules in EUD-NIC-HPβCD-IC-NF. More importantly, EUD-NIC-HPβCD-IC-NF was quite effective for preventing the release of NIC in the stomach in contrast to EUD-NIC-NF, which has already released more than half amount of NIC in 120 min. In conclusion, this study might open new areas for developing targeted delivery systems by the combination of nanofibers and CD-ICs for hydrophobic drugs such as NIC.

Eco-friendly bioadsorbent-based polymer composites as a pH-responsive material for selective removal of anionic and azo dyes from aqueous solutions

There is an urgent requirement to develop excellent dye adsorbent, which contains high dye removal capacity with desirable separation property which are imperative to remove anionic and azo dyes from aqueous solutions. To address this issue, novel polymer composites were synthesized with varying reaction parameters, owing to the fact that various grades of graft polymer composites have been optimized. As-synthesized bioadsorbent materials were examined in details by FT-IR, XRD, TGA, SEM-EDX, and VSM. The factors affecting the dye adsorption performance, including the effect of initial dye concentration, adsorbent dosage, treatment time, pH as well as recycling data, were systematically investigated. The reusability test shows that polymer composite can be renewed easily with HCl/NaOH solution as an efficient adsorbent for practical wastewater treatment. The conditions depending on adsorption equilibrium consistent with Langmuir isotherm model and pseudo-second-order kinetic model are the predominant models to describe the experimental data well. Henceforth, this work provided a unique strategy for the design of low-cost bioadsorbent, which can be utilized with grafting various monomers to get features pH-responsive polymer composites for removing targeted emerging dyes from aqueous solutions with rapid and high-adsorption efficiency. Graphical 1:A Schematic representation of the targeted dye removal process of chitosan-(acrylic acid-co-APTAC-co-DACPB)/Fe3O4 grafted polymer composites from aqueous solution.

Grafting with RAFT-gRAFT Strategies to Prepare Hybrid Nanocarriers with Core-shell Architecture.

Stimuli-responsive polymer materials are used in smart nanocarriers to provide the stimuli-actuated mechanical and chemical changes that modulate cargo delivery. To take full advantage of the potential of stimuli-responsive polymers for controlled delivery applications, these have been grafted to the surface of mesoporous silica particles (MSNs), which are mechanically robust, have very large surface areas and available pore volumes, uniform and tunable pore sizes and a large diversity of surface functionalization options. Here, we explore the impact of different RAFT-based grafting strategies on the amount of a pH-responsive polymer incorporated in the shell of MSNs. Using a “grafting to” (gRAFT-to) approach we studied the effect of polymer chain size on the amount of polymer in the shell. This was compared with the results obtained with a “grafting from” (gRAFT-from) approach, which yield slightly better polymer incorporation values. These two traditional grafting methods yield relatively limited amounts of polymer incorporation, due to steric hindrance between free chains in “grafting to” and to termination reactions between growing chains in “grafting from.” To increase the amount of polymer in the nanocarrier shell, we developed two strategies to improve the “grafting from” process. In the first, we added a cross-linking agent (gRAFT-cross) to limit the mobility of the growing polymer and thus decrease termination reactions at the MSN surface. On the second, we tested a hybrid grafting process (gRAFT-hybrid) where we added MSNs functionalized with chain transfer agent to the reaction media containing monomer and growing free polymer chains. Our results show that both modifications yield a significative increase in the amount of grafted polymer.

PH-responsive lipid polymer hybrid nanoparticles (LPHNs) based on poly (β-amino ester) as a promising candidate to resist breast cancers

Effective delivery of anti-tumor drugs to the tumor site remain a challenging issue, such as insufficient uptake by tumor cells, degradation by lysosomes and insufficient drug release. Therefore, it is crucial to utilize smart nanoparticles (NPs) designed with the ability to target the tumor site and respond to the unique microenvironment of the tumor tissue. In this paper, we prepared a novel pH responsive core-shell lipid polymer NPs (FA/PBAE/DTX-NPs). The NPs are composed of a mixed lipid shell (DSPE-PEG2000, FA-DSPE-PEG2000 and lecithin) and a polymer core (poly (β-amino ester), PBAE) for targeted delivery of docetaxel (DTX) to breast cancer. FA-PBAE/DTX-NPs had uniform particle size and excellent physical stability. The study of drug release in vitro showed that FA/PBAE/DTX-NPs could release DTX on demand under different pH.Blank NPs were considered nontoxic, while drug-loaded NPs have strong cytotoxicity to 4T1 cells in vitro. The tertiary amine group of PBAE enhanced endosomal/lysosomal escape of the NPs via the proton sponge effect, which triggers the rapid release of DTX. What's more, in vivo experiments have shown that FA/PBAE/DTX-NPs have favorable targeting, antitumor effect, and minimal systemic toxicity in tumor-bearing mice. To sum up, FA/PBAE/DTX-NPs could be selected as a candidate to delivery drug for breast cancer and improving the efficacy of chemotherapy.

PH-Responsive Polyketone/5,10,15,20-Tetrakis-(Sulfonatophenyl)Porphyrin Supramolecular Submicron Colloidal Structures.

In this work, we prepared color-changing colloids by using the electrostatic self-assembly approach. The supramolecular structures are composed of a pH-responsive polymeric surfactant and the water-soluble porphyrin 5,10,15,20-tetrakis-(sulfonatophenyl)porphyrin (TPPS). The pH-responsive surfactant polymer was achieved by the chemical modification of an alternating aliphatic polyketone (PK) via the Paal–Knorr reaction with N-(2-hydroxyethyl)ethylenediamine (HEDA). The resulting polymer/dye supramolecular systems form colloids at the submicron level displaying negative zeta potential at neutral and basic pH, and, at acidic pH, flocculation is observed. Remarkably, the colloids showed a gradual color change from green to pinky-red due to the protonation/deprotonation process of TPPS from pH 2 to pH 12, revealing different aggregation behavior.

Partition of spiramycin in a recyclable aqueous two-phase system based on pH-responsive and thermosensitive polymers

Aqueous two-phase systems have been widely studied for the separation and recovery of bioproducts. In this study, the thermosensitive polymer EO30PO70 and pH-responsive polymers (PADB4.66 and PADB6.26) were used to develop a recyclable aqueous two-phase system suitable for spiramycin partitioning. EO30PO70 represents poly-(ethylene oxide-propylene oxide), where 30 and 70 indicate the proportions of ethylene oxide and propylene oxide, respectively. PADB4.66 and PADB6.26 represent poly-(acrylic acid-dimethylamine ethyl methacrylate-butyl methacrylate), where the numbers (4.66 and 6.26) in the subscripts indicate the isoelectric point of the polymers. The phase separation mechanism of ATPS was studied through low-field nuclear magnetic resonance (LF-NMR) and surface tension. Moreover, the parameters affecting spiramycin partitioning, such as system components and composition, pH, temperature, and type and concentration of additive salt, were investigated. The best partitioning conditions were determined using 4.70% PADB6.26 and 31.67% EO30PO70 in the presence of 0.05 mol/L NaSCN at 35 °C and pH = 9.2. The highest partition coefficient of spiramycin from fermentation broth was 11.92, with an extraction recovery of 97.69%. In addition, phase-forming polymers PADB6.26 and EO30PO70 could be recovered by regulating the pH or temperature, and their recoveries reached 92.39% and 98.76%, respectively.

Glucose- and pH-Responsive Supramolecular Polymer Vesicles Based on Host-Guest Interaction for Transcutaneous Delivery of Insulin.

Smart insulin delivery platforms having the ability of mimicking pancreatic cells are highly expected for diabetes treatment. Herein, a smart glucose-sensitive insulin delivery platform on the basis of transcutaneous microneedles has been designed. The as-prepared microneedles are composed of glucose- and pH-responsive supramolecular polymer vesicles (PVs) as the drug storage and water soluble polymers as the matrix. The well-defined PVs are constructed from the host-guest inclusion complex between water-soluble pillar[5]arene (WP5) with pH-responsiveness and paraquat-ended poly(phenylboronic acid) (PPBA-G) with glucose-sensitivity. The drug-loaded PVs, including insulin and glucose oxidase (GOx) can quickly respond to elevated glucose level, accompanied by the disassociation of PVs and fast release of encapsulated insulin. Moreover, the insulin release rate is further accelerated by GOx, which generates gluconic acid at high glucose levels, thus decreasing the local pH. Therefore, the host-guest interaction between WP5 and PPBA-G is destroyed and a total structure disassociation of PVs takes place, contributing to a fast release of encapsulated insulin. The in vivo insulin delivery to diabetic rats displays a quick response to hyperglycemic levels and then can fast regulate the blood glucose concentrations to normal levels, which demonstrates that the obtained smart insulin device has a highly potential application in the treatment of diabetes.

PH-responsive Ag2S nanodots loaded with heat shock protein 70 inhibitor for photoacoustic imaging-guided photothermal cancer therapy

Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive Ag2S nanodots (Ag2S NDs) loaded with HSP70 inhibitor (QE-PEG-Ag2S) for enhanced photothermal cancer therapy. QE-PEG-Ag2S was easily prepared via self-assembly of hydrophobic Ag2S NDs, amphiphilic pH-responsive PEG5k-PAE10k polymer, and an HSP70 inhibitor quercetin (QE). QE-PEG-Ag2S has ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The slightly acidic environment of tumor cells and the acidity of lysosomes as well as the high temperature generated by photothermal therapy under irradiation of NIR light (808 nm) promote the release of the inhibitor molecules to reduce the heat resistance of cancer cells and improve the in vivo photothermal therapy efficiency. Moreover, QE-PEG-Ag2S has good photoacoustic imaging (PAI) ability; this QE-PEG-Ag2S concentration dependent signal can precisely follow the accumulation of the nanomaterials in tumors and dictate the correct time for light therapy. As a result, QE-PEG-Ag2S achieved complete tumor ablation effect with no recurrence when only irradiated with NIR light for 10 min. This approach offers a new approach for the theranostic applications of Ag2S NDs. Statement of SignificanceIn this work, pH-responsive Ag2S nanodots loaded with the heat shock protein inhibitor for enhanced photothermal cancer therapy have been simply prepared via self-assembly process. This nanoagent possesses ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The acidic environment of tumor cells and the acidity of lysosomes, as well as the high temperature generated by photothermal therapy under irradiation of NIR light promote the release of the inhibitor molecules from the nanoagent to improve the in vivo photothermal therapy efficiency. Moreover, the photoacoustic imaging (PAI) of the nanoagent can precisely follow the accumulation of the nanomaterials in tumors and dictate the light therapy time to guarantee the complete tumor ablation effect with no recurrence.

A pH-responsive polymer linked with immunomodulatory drugs: synthesis, characteristics and in vitro biocompatibility.

Cancer immunotherapy is a promising method for cancer therapy. Imiquimod (R837) is a molecule that could activate immune systems for cancer immunotherapy, but an easily manufactured biocompatible carrier to deliver R837 may be needed to overcome the disadvantages of R837. Micelles formed by biocompatible copolymers have been widely used to deliver chemotherapeutic drugs but not immunotherapeutic drugs. In this study, R837 was linked to an amphiphilic biodegradable copolymer mPEG-b-PLA via acid-sensitive Schiff bases. The molecular structures were investigated by 1 H nuclear magnetic resonance, gel permeation chromatography and Fourier transform infrared spectroscopy. The product could be self-assembled into micelles with R837 content as high as 22.4%. Owing to acid-cleavable Schiff bases, the release of R837 from micelles was markedly accelerated under acidic media. Consequently, the micelles linked with R837 stimulated the expression of major histocompatibility complex II-stimulating molecules on the surface of RAW 264.7 macrophages at pH 6.5 but not pH 7.4. By using human umbilical vein endothelial cells as the in vitro model, it was shown that the polymer carriers and R837-linked micelles were minimally cytotoxic and did not induce the activation of endothelial cells under physiological pH, which suggested the relatively high biocompatibility. In conclusion, this study successfully developed pH-responsive immunotherapeutic drug-loaded micelles that could activate macrophages at acidic pH in vitro. The high biocompatibility of the micelles to endothelial cells also indicated the potential uses under in vivo conditions.

PH-responsive intramolecular FRET-based self-tracking polymer prodrug nanoparticles for real-time tumor intracellular drug release monitoring and imaging.

An intramolecular fluorescence resonance energy transfer (FRET)-based macromolecular theranostic prodrug was designed by directly conjugating Doxorubicin (DOX) as the FRET acceptor onto the naphthalimide side groups in the fluorescent copolymer PPEGMA20-PNAP8 as the FRET energy donor via an acid-labile imine bond, without a fluorogenic linker. The proposed PPEGMA20-PNAP8-DOX theranostic prodrug showed a high DOX content of 24.3% owing to a conjugation efficiency of>93% under mild conjugation conditions. It could easily self-assemble into unique theranostic nanoparticles with a Dh of 71nm. The theranostic nanoparticles showed excellent pH-triggered DOX release performance with very low premature drug leakage of 6.3% in normal physiological medium over 129h, while>91% of the conjugated DOX was released in the acidic tumor intracellular microenvironment. MTT assays indicated the enhanced antitumor efficacy of the proposed theranostic nanoparticles compared with free DOX. Furthermore, because drug release was triggered by pH, orange fluorescence was restored to the blue fluorescence of the backbone copolymer. Such self-tracking pH-responsive colorful fluorescence variations during intracellular drug delivery and release are expected to allow real-time tumor intracellular drug release monitoring and imaging diagnosis.

A Comparative Study on the Effect of Hydroxypropyl Methylcellulose F4M and Eudragit<sup>®</sup> E PO on the Physicochemical Properties of Taste-Masking Microparticles

The objective of this study was to investigate the effect of polymers and their content level on the taste-masking efficiency of spray-dried microparticles. Diclofenac sodium (DS) was used as a model drug, owing to its bitter taste. Hydroxypropyl methylcellulose F4M (HPMC F4M) and Eudragit® E PO were involved in the study as a hydrophilic and a pH-responsive polymer, respectively. The taste-masked DS microparticles with the drug:polymer ratios of 1:1, 1:2 and 1:4 were prepared by the spray-drying technique. The collapsed hollow sphere HPMC F4M based-microparticles was observed meanwhile spray-dried Eudragit® E PO based-microparticles were spherical. Loading capacity of both polymer based-microparticles decreased regarding to the increment of drug:polymer ratio. The Eudragit® E PO based-microparticle in the ratio of 1:4 provided the highest loading efficiency as 91.97%. According to the simplified dissolution testing, the taste-masking ability of HPMC F4M and Eudragit® E PO based-microparticles increased upon the increase of drug:polymer ratio. Drug release at the first 5 minutes from dissolution profiles, tested by type II dissolution apparatus, of the Eudragit® E PO based-microparticles was delayed compared to HPMC F4M based-microparticles. Therefore, it could be assumed that Eudragit® E PO was a promising taste-masking polymer for DS with a pleasant taste.

Design of pH-responsive SAP polymer for pore solution chemistry regulation and crack sealing in cementitious materials

The crack development is considered to be one of the most severe threats to the durability of concrete infrastructure. This study aims to enhance the durability performance of cementitious material with the pH-responsive Superabsorbent Polymer (SAP). The SAP was synthesized with acrylic acid (AA)-methyl acrylate (MA) precursors, and three type samples with different crosslinking levels were prepared. The examination on the pH sensitivity indicated that the swelling capacity of the prepared SAP would first increase and then decrease with solution alkalinity, and the peak swelling potential was achieved around pH value of 12 for all the three type SAP with solution/gel mass ratio of 500. Further examination indicated the alkalinity of the buffer solution was reduced during the adsorption test, which can be caused by the hydrolysis of the amide groups and the crosslinker. Besides that, it was also found the solution/gel ratio and the Ca(OH)2 content could affect the swelling potential of the SAP. After that, the performance tests were conducted for the evaluation of concrete with SAP. A wax-coating protocol for the SAP was designed by using the hot-water method to prevent its swelling during mixing process. It was found that the strength reduction for samples with wax-coated SAP was insignificant compared to that of the control samples. Furthermore, durability tests supported the wax-shell could be broken by the crack propagation in concrete. And further experimental studies are needed to optimize the wax-size and shell thickness for enhanced self-sealing efficiency.

Study of Microbial Transglutaminase Partitioning in Thermo-pH-Responsive Aqueous Two-Phase Systems.

The recyclable aqueous two-phase systems (ATPS) responding to environmental stimuli have been widely studied in the purification of biologics. In this study, a thermo-responsive polymer PNE was copolymerized after optimization of monomer ratio. In addition, its lower critical solution temperature (LCST, 31°C) and first recovery (99.43%) were determined. Then, PNE was used to form two recyclable ATPS with another thermo-responsive polymer PNDBN and a pH-responsive polymer PADB4.91, which were polymers already prepared in the lab. Meanwhile, the partition behavior of microbial transglutaminase (MTG) was explored using these two ATPS. The result showed that the PNE/PADB4.91 ATPS was superior to PNDBN/PNE ATPS owing to its faster phase formation and better partition performance. In order to optimize the partition behavior, several parameters were investigated based on PNE/PADB4.91 ATPS. In the ATPS constructed with 2.5% (w/v) PNE and 3.5% (w/v) PADB4.91, the maximal partition coefficient (1/KE) and enzymatic recovery (ERB) of MTG were 12.9 and 95.21% in the presence of 10mM KCl when the temperature, pH, and the addition amount of MTG were 25°C, 7.0, and 2mg/mL, respectively.

Dual Photo- and pH-Responsive Spirooxazine-Functionalized Dextran Nanoparticles.

A dual photo- and pH-responsive spirooxazine-functionalized polymer was synthesized by functionalization of dextran with a spirooxazine derivative (SO-COOH). The functionalized dextran derivatives can form nanoparticles in aqueous medium. Under UV light irradiation, the spirooxazine-functionalized dextran (Dex-SO) nanoparticles isomerize to zwitterionic merocyanine-functionalized dextran (Dex-MC), which leads to aggregation. However, the process is reversible upon irradiation with visible light. Under acidic conditions, the hydrophobic spirooxazine is protonated, and the nanoparticles aggregate or swell at pH values of 5 or 3, respectively. The encapsulation of the hydrophobic fluorescent dye Nile Red as model drug allowed us to gain more information about the structural changes under stimulation of UV light and acid treatment.

Carbon nanotube embedded cyclodextrin polymer derived injectable nanocarrier: A multiple faceted platform for stimulation of multi-drug resistance reversal

A combination of cocktail chemotherapy (CCT), photothermal therapy (PTT) and inhibition of angiogenesis was investigated as an effective approach to combat major challenges of multidrug resistance and non-targeted drug delivery encountered in conventional cancer therapy. An injectable nanocarrier was developed through functionalization of carbon nanotubes (CNTs) with rationally modified carbohydrate (β-Cyclodextrin-CD) derived pH and thermo responsive polymer. Embedding CNT to CD polymer offers a nanocarrier which effectively demonstrated CCT, high NIR triggered photothermal efficiency, anti-angiogenic potential for selective tumor homing as well as enhanced multi-drug resistance (MDR) reversal with minimal toxic effects on normal cells. The simultaneously loading with curcumin and doxorubicin hydrochloride exhibited synergistic effect for triggering antitumor effect in vitro and demonstrated down regulation of growth factors associated with angiogenesis ex-ovo. In-vivo studies ascertained that the nanocarrier synthesized with the rational for MDR reversal can lead to enhanced cancer cell death via multiple approaches.

Temperature- and pH-Responsive Star Polymers as Nanocarriers with Potential for in Vivo Agrochemical Delivery.

Climate change is increasing the severity and length of heat waves. Heat stress limits crop productivity and can make plants more sensitive to other biotic and abiotic stresses. New methods for managing heat stress are needed. Herein, we have developed ∼30 nm diameter poly(acrylic acid)-block-poly(N-isopropylacrylamide) (PAA-b-PNIPAm) star polymers with varying block ratios for temperature-programmed release of a model antimicrobial agent (crystal violet, CV) at plant-relevant pH. Hyperspectral-Enhanced Dark field Microscopy was used to investigate star polymer-leaf interactions and route of entrance. The majority of loaded star polymers entered plant leaves through cuticular and epidermis penetration when applied with the adjuvant Silwet L-77. Up to 43 wt % of star polymers (20 μL at 200 mg L-1 polymer concentration) applied onto tomato (Solanum lycopersicum) leaves translocated to other plant compartments (younger and older shoots, stem, and root) over 3 days. Without Silwet L-77, the star polymers penetrated the cuticle, but mainly accumulated at the epidermis cell layer. The degree of the star polymer temperature responsiveness for CV release in vitro in the range of 20 to 40 °C depends on pH and the ratio of the PAA to PNIPAm blocks. Temperature-responsive release of CV was also observed in vivo in tomato leaves. These results underline the potential for PAA-b-PNIPAm star polymers to provide efficient and temperature-programmed delivery of cationic agrochemicals into plants for protection against heat stress.

Multifunctional Nanomodulators Regulate Multiple Pathways To Enhance Antitumor Immunity.

Immunosuppression is a key factor leading to a low therapeutic efficiency of the currently used immunotherapies. Monotherapies are unable to overcome immunosuppression because of the complex interplay of immune cells in tumors. Herein, we report a multifunctional nanomodulator (MFNM) as a carrier to deliver different types of immune modulators for comodulating multiple pathways. An MFNM has a core-shell structure, in which small-molecule drugs are encapsulated in a mesoporous silica nanoparticle (MSN) core with a pH-responsive polymer layer. Further, the polymeric shell provides active sites that are readily modifiable by multiple types of antibodies to regulate the immune-related processes. By codelivering cyclophosphamide (CTX), αPD-L1 (B7-H1), and α4-1BB (CD137L) monoclonal antibodies (mAbs) to tumors, an MFNM has been shown to regulate multiple immune pathways and enhance an antitumor immunity. As antibodies and small-molecule drugs loaded in an MFNM can be modified based on the tumor type, the MFNM provides a feasible platform for the development of advanced immunotherapies that require simultaneous modulation of multiple biological processes.

Synthesis of a new triple-responsive biocompatible block copolymer: Self-assembled nanoparticles as potent anticancer drug delivery vehicle

There has been a continuous effort towards a synthesis of new stimuli-responsive polymer nanoparticle systems for improved cancer chemotherapy over the last decade. In this context, we have presently developed a temperature, pH, and redox-responsive amphiphilic block-copolymer capable of forming nanoparticles in the aqueous medium, targeted towards drug delivery applications. The copper-catalyzed azide-alkyne cycloaddition reaction was utilized to tie the ends of two copolymers - a thermo-responsive poly(N-isopropylacrylamide) based copolymer with an azide end group and a pH-responsive hydrophobic polymer with redox responsive disulfide bond and an alkyne end group, producing a new triple responsive amphiphilic block copolymer (PHNP) that self-assemble in water to produce nanoparticles. Upon heating above the cloud point of poly(N-isopropylacrylamide), these nanoparticles experienced further aggregation to produce larger sized particles as measured by dynamic light scattering, UV–visible spectroscopy, and scanning electron microscopy techniques. PHNP was found to be capable of encapsulating drugs like doxorubicin (DOX) and also fluorescent probes alike Nile Red. The drug release kinetics divulged that in a period of 24 h more than 90% of the encapsulated DOX was released in pH 5.4 buffer having 10 mM glutathione (GSH) at 40 °C, an environment prevailing in cancer tissues. In vitro studies including live-dead assay and rhodamine-DAPI staining showed that PHNP was non-cytotoxic. DOX-loaded PHNP was observed to be more effective in prohibiting bone cancer cell (MG63) line in comparison to free DOX, demonstrated by the significant reduction of IC50 values. The uptake studies showed that DOX-encapsulated PHNP was more effective for morphometric distortion of MG63 cells in comparison to bare DOX. Therefore, the present research on the development of a biocompatible thermal, pH, and redox-responsive polymer opens up new opportunities in the area of polymeric carrier systems for drug delivery to cancer cells.