Efficient Anticancer Drug Delivery Research Articles

Efficient delivery of anticancer drugs using functionalized-Ag-decorated Fe3O4@SiO2 nanocarrier with folic acid and β-cyclodextrin

Nanocarrier surface functionalization has been widely regarded as a promising approach for achieving precise and targeted drug delivery systems. In this work, the fabrication of functionalized-Ag-decorated Fe3O4@SiO2 (Fe3O4@SiO2-Ag) nanocarriers with folic acid (FA) and β-cyclodextrin (BCD) exhibit a remarkable capacity for delivering two types of anticancer drugs, i.e., doxorubicin (DOX) and epirubicin (EPI), into cancer cells. The effective functionalization of Fe3O4@SiO2-Ag nanoparticles has been achieved through the use of cysteine (Cys) as an anchor for attaching FA and BCD via EDC-NHS coupling and Steglich esterification methods, respectively. The findings indicate that surface functionalization had no significant impact on the physicochemical characteristics of the nanoparticles. However, it notably affected DOX and EPI loading and release efficiency. The electrostatic conjugation of DOX/EPI onto the surface of Fe3O4@SiO2-Ag/Cys/FA and Fe3O4@SiO2-Ag/Cys/BCD exhibited maximum loading efficiency of 50–60% at concentration ratio of DOX/EPI to nanoparticles of 1:14. These nanocarriers also achieved an 40–47% DOX/EPI release over 36 days. Furthermore, the drug-loaded functionalized-nanocarrier showed cytotoxic effects on SK-MEL-2 cells, as demonstrated by an in vitro MTT assay. This suggests that the as-prepared functionalized-nanoparticles have promise as a carrier for the efficient anticancer drugs.

PSMA-targeted dendrimer as an efficient anticancer drug delivery vehicle for prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men in the United States. Although early-stage treatments exhibit promising 5-year survival rates, the treatment options for advanced stage disease are constrained, with short survival benefits due to the challenges associated with effective and selective drug delivery to PCa cells. Even though targeting Prostate Specific Membrane Antigen (PSMA) has been extensively explored and is clinically employed for imaging and radio-ligand therapy, the clinical success of PSMA-based approaches for targeted delivery of chemotherapies remains elusive. In this study, we combine a generation 4 hydroxy polyamidoamine dendrimer (PD) with irreversible PSMA ligand (CTT1298) to develop a PSMA-targeted nanoplatform (PD-CTT1298) for selective intracellular delivery of potent chemotherapeutics to PCa. PD-CTT1298-Cy5 exhibits a PSMA IC50 in the nanomolar range and demonstrates selective uptake in PSMA (+) PCa cells via PSMA mediated internalization. When systemically administered in a prostate tumor xenograft mouse model, PD-CTT1298-Cy5 selectively targets PSMA (+) tumors with significantly less accumulation in PSMA (-) tumors or upon blocking of the PSMA receptors. Moreover, the dendrimer clears rapidly from the off-target organs limiting systemic side-effects. Further, the conjugation of an anti-cancer agent, cabozantinib to the PSMA-targeted dendrimer translates to a significantly enhanced anti-proliferative activity in vitro compared to the free drug. These findings highlight the potential of PD-CTT1298 nanoplatform as a versatile approach for selective delivery of high payloads of potent chemotherapeutics to PCa, where dose related systemic side-effects are a major concern.

Gold nanoparticles in transferrin-targeted dual-drug delivery in vitro

Nanotechnology has significantly impacted medicine by improving diagnostics and therapeutics. By modifying materials at the nanoscale, we can impart unique and desirable characteristics to the nanoparticles (NPs), which are not present in their bulk counterparts. Gold NPs (AuNPs) have emerged as potential vehicles for drug delivery due to their favourable attributes, such as low toxicity, high surface area, high loading capacity, biocompatibility, ease of synthesis, and surface modification. Although anticancer drugs are effective, they are rapidly metabolized in the body after administration, reducing their effectiveness in addition to inducing severe side effects. Hence, this study aimed to address the need for a safe and effective drug delivery system that will ensure controlled drug release to the desired tumour site. In this study, AuNPs were chemically synthesized, conjugated to the targeting ligand, transferrin and loaded with a dual-drug formulation of doxorubicin (DOX) and 5-fluorouracil (5-FU) encapsulated within a chitosan (CS) matrix. Characterization revealed that the AuNPs were spherical in shape, with a good size distribution in the range of 54.9 ± 7.5 nm. The encapsulation efficiency was calculated to be 72.63 % for 5-FU and 74.81 % for DOX, which implied a higher therapeutic load for delivery to the cancer cells. Drug release studies revealed a controlled drug release profile, with 5-FU encapsulated CS-Tf-AuNPs and DOX encapsulated CS-Tf-AuNPs releasing 82.31 % and 80.86 % of 5-FU and DOX, respectively, over 72 h, while the dual drug encapsulated CS-Tf-AuNPs generated a release of 77.33 % 5-FU and 75.60 % DOX over the same period. In vitro cytotoxicity in the human cancer cell lines, HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), and the non-cancer HEK293 (embryonic kidney) revealed a specificity of the nanocomplexes to the cancer cells, with little or no significant toxicity observed in the non-cancer cells. The transferrin-targeted nanocomplexes exhibited greater anticancer activity than their non-targeted counterparts. These results highlight the potential of these targeted dual-drug AuNP nanocomplexes in providing safe and efficient delivery of anticancer drugs with reduced side effects in vitro.

The folate-chitosan-decorated harmaline nanostructured lipid carrier (FCH-NLC), the efficient selective anticancer nano drug delivery system

The folate-chitosan-decorated harmaline nanostructured lipid carrier (FCH-NLC), the efficient selective anticancer nano drug delivery system

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.

Transporter-mediated drug resistance is a major obstacle in anticancer drug delivery and a key reason for cancer drug therapy failure. Membrane solute carrier (SLC) transporters play a crucial role in the cellular uptake of drugs. The expression and function of the SLC transporters can be down-regulated in cancer cells, which limits the uptake of drugs into the tumor cells, resulting in the inefficiency of the drug therapy. In this review, we summarize the current understanding of low-SLC-transporter-expression-mediated drug resistance in different types of cancers. Recent advances in SLC-transporter-targeting strategies include the development of transporter-utilizing prodrugs and nanocarriers and the modulation of SLC transporter expression in cancer cells. These strategies will play an important role in the future development of anticancer drug therapies by enabling the efficient delivery of drugs into cancer cells.

AIE-Featured Redox-Sensitive Micelles for Bioimaging and Efficient Anticancer Drug Delivery.

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.

A Novel Thermal-driven Self-assembly Method to Prepare Albumin Nanoparticles: Formation Kinetics, Degradation Behavior and Formation Mechanism.

Nanoparticles based on bovine serum albumin (BSA), which shares 76% homology with human serum albumin (HSA), have emerged as a promising candidate for the efficient delivery of anticancer drugs. Thermal-driven self-assembly is a novel organic solvent-free approach to produce albumin nanoparticles. In our previous study, some features of this nanoparticle such as drug loading efficiency, drug encapsulation efficiency and drug release kinetics have been evaluated. However, the formation mechanism that determines the above nanoparticle properties remains unclear. Here, we investigated the formation kinetics and mechanism using spectroscopic methods including fluorescence spectroscopy, circular dichroism (CD) and differential scanning calorimetry (DSC). We also applied chemical analysis methods that measured the content changes of albumin active groups and vanillin. To verify the covalent networks in the nanoparticles, trypsin and glutathione (GSH) were used separately to cleave the peptide bonds and disulfide bridges, and dynamic light scattering (DLS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were used to analyze the degraded samples. BSA nanoparticles started to form at 10min and were completely formed at 120min. With the digestion of trypsin, more than 50% of the nanoparticles were degraded within 60min. CD spectra showed that α-helical structure of BSA decreased from 42.3% to 39.8% and 37.7% after heating for 10 and 60min, respectively. In the DSC thermogram, the melting peak of BSA nanoparticles was 229.14℃, which is about 12℃ higher than the physical mixture of BSA and vanillin, indicating that chemical reactions occurred during the nanoparticle formation and formed a new more stable substance. Moreover, the results of active group assay, GSH degradation and SDS-PAGE experiments also proved that disulfide bonds and peptide bonds were formed between BSA molecules, whereas Schiff bases were formed between BSA and vanillin molecules. Formation kinetics and degradation behavior are important properties to characterize albumin nanoparticles and should be paid attention to. Not only that, this study also provides an effective way to study the formation mechanism of protein-based nanodrug delivery systems.

Before in vivo studies: In vitro screening of sphingomyelin nanosystems using a relevant 3D multicellular pancreatic tumor spheroid model

Sphingomyelin nanosystems have already shown to be promising carriers for efficient delivery of anticancer drugs. For further application in the treatment of pancreatic tumor, the investigation on relevant in vitro models able to reproduce its physio-pathological complexity is mandatory. Accordingly, a 3D heterotype spheroid model of pancreatic tumor has been herein constructed to investigate the potential of bare and polyethylene glycol-modified lipid nanosystems in terms of their ability to penetrate the tumor mass and deliver drugs. Regardless of their surface properties, the lipid nanosystems successfully diffused through the spheroid without inducing toxicity, showing a clear safety profile. Loading of the bare nanosystems with a lipid prodrug of gemcitabine was used to evaluate their therapeutic potential. While the nanosystems were more effective than the free drug on 2D cell monocultures, this advantage, despite their efficient penetration capacity, was lost in the 3D tumor model. The latter, being able to mimic the tumor and its microenvironment, was capable to provide a more realistic information on the cell sensitivity to treatments. These results highlight the importance of using appropriate 3D tumor models as tools for proper in vitro evaluation of nanomedicine efficacy and their timely optimisation, so as to identify the best candidates for later in vivo evaluation.

Dual-Responsive Alginate Hydrogel Constructed by Sulfhdryl Dendrimer as an Intelligent System for Drug Delivery.

Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.

Biocompatible thermoresponsive N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide-based random copolymer: synthesis and studies of its composition dependent properties and anticancer drug delivery efficiency.

A new acrylamide monomer, N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide (M3i), consisting of both isopropyl and isopropylamidopropyl moieties, has been synthesized from isopropylamine and N-isopropylacrylamide via an aza-Michael addition reaction followed by amidation with acryloyl chloride. The homopolymer of M3i (polyM3i) and a series of random copolymers of M3i and poly(ethylene glycol)methyl ether acrylate (PEGA: CH2CHCO2(CH2CH2O)nMe, Mn = 480, n = 9 on average) with varying compositions have been synthesized via reversible addition-fragmentation chain transfer polymerization using 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as well as 1-phenylethyl phenyl dithioacetate (PEPD) as a RAFT agent. These polymers have been characterized by 1H NMR, FTIR, GPC, UV-Vis, fluorescence, TGDTA, DSC, DLS, and TEM techniques. A lower critical solution temperature (LCST) and glass transition temperature (Tg) for polyM3i prepared using DDMAT were observed at 17 and 133 °C, respectively, while for a polymer formed using PEPD, no LCST was observed until 0 °C and its observed Tg was found at 127.3 °C. The polymers are thermally stable up to 300 °C. Upon an increase in the M3i content in the copolymers, LCST decreases, Tg increases, and the apparent hydrodynamic diameter decreases. Moreover, the effects of concentration and the addition of urea and sodium chloride on the LCST of the copolymer with an LCST close to body temperature were studied. Owing to the incorporation of PEGA, a higher critical micellar concentration and larger TEM particle size of this copolymer were observed with respect to those of polyM3i. The usefulness of the micelles of the copolymers as nano-carriers for the drug doxorubicin was explored. The in vitro tumoricidal activity of the micelles of the doxorubicin-loaded copolymers was also assessed against Dalton's lymphoma cells.

Prostate-Specific Membrane Antigen and Esterase Dual Responsive Camptothecin-Oligopeptide Self-Assembled Nanoparticles for Efficient Anticancer Drug Delivery.

BackgroundThe clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy.Methods and ResultsIn this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo.ConclusionCPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery.

Preparation and antitumor activity of triphenylphosphine-based mitochondrial targeting polylactic acid nanoparticles loaded with 7-hydroxyl coumarin.

Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by 1H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery.

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

PH-tunable nanoparticles composed of copolymers of lactide and allyl-glycidyl ether with various functionalities for the efficient delivery of anti-cancer drugs

The designing of biocompatible nanocarriers for the efficient delivery of their cargos to the desired targets remains a challenge. In this regard, the most promising strategy relies on the construction of pH- or thermo-responsive nanoparticles (NPs). However, it is also important to preserve the balance between the responsiveness of the carrier and their stability in physiological conditions. Therefore, we described a new family of copolymers of lactide and allyl-glycidyl ether which were subsequently modified by thiol-ene reaction to functionalize the resulting copolymer with acetylcysteine (ACC) or thioglycolic acid (tGA) moieties. Subsequently, these copolymers were used to obtain blank and doxorubicin (DOX) loaded NPs with an average diameter of about 50−100 nm. Interestingly, the NPs were stable in different pH conditions, however, the presence of ACC or tGA units in the polymeric chain allows for the reduction of the undesired burst release due to the supramolecular interactions between polymeric pedant groups and DOX. The release tests of DOX from NPs showed that DOX release rate decrease depending on the pH values and the copolymer functionalization in order of non-modified NPs > ACC-modified NPs > tGA functionalized NPs. Most importantly, the MTT assay showed that all blank NPs are non-toxic against the normal L929 cell line. Subsequently, the antitumor efficiency of the obtained NPs was tested towards L929 (murine fibroblast cell line), HeLa (cervical cancer), and AGS (human gastric adenocarcinoma cancer) cells. The results demonstrated that DOX-loaded NPs efficiently induce the reduction in the viability of the HeLa and AGS cell, and this reduction in the viability was even below 20 % for the AGS cells. Together with their biocompatibility, the obtained NPs offer a novel route for the preparation of nanocarriers for the controlled and efficient delivery of anticancer drugs.

Nanoscale Metal-Organic Frameworks That are Both Fluorescent and Hollow for Self-Indicating Drug Delivery.

Nanoscale metal-organic frameworks (MOFs) that are both fluorescent and hollow are attracting increasing interest in recent years, but ideal candidates prepared by reliable methods for biomedical applications are still very limited. Herein, we for the first time prepared tetrakis[4-(4-carboxyphenyl)phenyl]ethene (TCBPE)-based MOF nanotubes with hollow nanostructures, which could emit strong fluorescence. It was further discovered that the formation of this hollow hexagonal nanotube underwent a self-templated growth and a subsequent concaving process, which revealed that the synthesis of this MOF was kinetic rather than thermodynamic. This new MOF showed high biocompatibility, optical stability, sensitivity to pH response, and capability for exotic loading. This new MOF was further employed for efficient anti-cancer drug delivery in a self-indicating manner based on these attractive features. Therefore, this work could bring in valuable insights into the exploration of multifunctional MOFs in the field of biomedical applications by providing a new exemplar with high practical utility.

Simple and feasible design of a polymeric nanoparticle for efficient anticancer drug delivery

In this paper, we present a simple and feasible drug self-assembled delivery system with pH responsiveness and targeting function for cancer therapy. The drug delivery system is composed of an anticancer drug and an amphiphilic random copolymer based on phenylboronic acid, galactose, and polyethylene glycol monomethyl ether acrylate molecules and achieved through reversible addition–fragmentation chain transfer polymerization. The micelles present targeting function by introducing galactose molecules and show pH sensitivity on the basis of the interactions between phenylboronic acid and galactose molecules. Particle size, transmission electron microscopy, and drug release assays show the pH-responsive behavior of micelles at pH 6.0. Cellular uptake assay demonstrates that micelles can internalize HepG2 cells via receptor-mediated interaction. In addition, the drug-loaded micelles can considerably inhibit cancer cell proliferation as indicated by in vivo antitumor assay. The synthesized micelles may facilitate the development of valid drug delivery systems for cancer therapy.

CRISPR-dCas9-Guided and Telomerase-Responsive Nanosystem for Precise Anti-Cancer Drug Delivery.

Nanodrug delivery systems are very promising for highly efficient anticancer drug delivery. However, the present nanosystems are commonly located in the cytoplasm and mediate uncontrolled release of drugs into cytosol, while a large number of anticancer drugs function more efficiently inside the nucleus. Here, we constructed a CRISPR-dCas9-guided and telomerase-responsive nanosystem for nuclear targeting and smart release of anticancer drugs. CRISPR-dCas9 technology has been employed to achieve conjugation of mesoporous silica nanoparticles (MSNs) with a high payload of the active anticancer drug, doxorubicin (DOX). A specifically designed wrapping DNA was used as a telomerase-responsive biogate to encapsulate DOX within MSNs. The wrapping DNA is extended in the presence of telomerase, which is highly activated in tumor cells, but not in normal cells. The extended DNA sequence forms a rigid hairpin-like structure and diffuses away from the MSN surface. CRISPR-dCas9 specifically targets telomere-repetitive sequences at the tips of chromosomes, facilitating the precise delivery of the nanosystem to the nucleus, and effective drug release triggered by telomerase that was enriched around telomeric repeats. This study provides a strategy and nanosystem for nuclear-targeted delivery and tumor-specific release of anticancer drugs that will maximize the efficiency of cancer cell destruction.

QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation.

Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% ± 0.5 and 6.82 ± 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies.

RAFT polymerization mediated core-shell supramolecular assembly of PEGMA-co-stearic acid block co-polymer for efficient anticancer drug delivery.

In this work, core–shell supramolecular assembly polymeric nano-architectures containing hydrophilic and hydrophobic segments were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. Herein, polyethylene glycol methyl ether methacrylate (PEGMA), and stearic acid were used to synthesize the poly(PEGMA) homopolymer and stearyl ethyl methacrylate (SEMA), respectively. Then, PEGMA and SEMA were polymerized through controlled RAFT polymerization to obtain the final diblock copolymer, poly(PEGMA-co-SEMA) (BCP). Model anticancer drug, doxorubicin (DOX) was loaded on BCPs. Interestingly, efficient DOX release was observed at acidic pH, similar to the cancerous environment pH level. Significant cellular uptake of DOX loaded BCP50 (BCP50-DOX) was observed in MDA-MB-231 triple negative breast cancer cells and resulted in a 35 fold increase in anticancer activity against MDA MB-231 cells compared to free DOX. Scanning electron microscopy (SEM) imaging confirmed the apoptosis mediated cellular death. These core–shell supramolecular assembly polymeric nano-architectures may be an efficient anti-cancer drug delivery system in the future.