Release Of Anticancer Drugs Research Articles

Epirubicin-loaded marine carrageenan oligosaccharide capped gold nanoparticle system for pH-triggered anticancer drug release

Gold nanoparticles (AuNPs) and the pH stimuli-responsive drug delivery system have been extensively applied in cancer treatment. Carrageenan derived from marine red algae shows a promising application prospect for drug delivery as a nanomaterial for its biodegradability, abundance, and non-toxicity. Carrageenan oligosaccharide (CAO) was used as a biocompatible reductant for green synthesis of CAO-AuNPs, and the obtained CAO-AuNPs were further used as a delivery system for pH-triggered delivery of epirubicin (EPI). The EPI-CAO-AuNPs were demonstrated to be spherical and homogeneous with mean diameter of 141 ± 6 nm by means of electron microscopy and Malvern particle size analyzer. Results showed that the release of EPI from EPI-CAO-AuNPs was significant under acidic condition that simulated cancer environment, while it was negligible under physiological pH in vitro. Confocal laser scanning microscope and flow cytometry analysis showed that EPI-CAO-AuNPs were localized in cellular nucleus and induced more apoptosis of HCT-116 and HepG2 cells than free EPI. A new pH-triggered anticancer drug release was achieved by EPI-CAO-AuNPs system for the first time. The developed EPI-CAO-AuNPs nanosystem shows a promising prospect for pH-triggered delivery of antitumor drugs, and our work provides a new idea for targeted drug delivery by using biocompatible marine carbohydrates as nanomaterial.

Plug-and-Play Continuous Gas Flow Assembly of Cysteine-Inserted AuCu Nanobimetals for Folate-Receptor-Targeted Chemo-Phototherapy.

Conjugatable nanobimetals exhibiting broadband light absorption for use as phototherapeutic platforms were assembled via a plug-and-play continuous gas flow route. Electrically produced AuCu nanobunches (NBs) under nitrogen gas flow were directly injected into cysteine (cys) solution through gas pressurization to mechanically spray the solution (AuCu into cys droplets). The sprayed droplets were then exposed to 185 nm UV light (higher photon energy [6.2 eV] than the work functions of Au [5.1 eV] and Cu [4.7 eV]) to initiate photoionization of AuCu NBs for subsequent electrostatic reaction with the SH- group of cys to form cys-inserted AuCu (AuCu-cys) platforms in a single-pass gas stream. These platforms exhibited broadband light absorption spectra because of hybridized interparticle plasmonic coupling and could be conjugated to folic acid (FA) when dispersed in FA solution to form highly dispersible, biocompatible, and cancer-targetable AuCu-cys-FA. This material was suitable for use in targeted phototherapy of folate-receptor (FR)-rich cancers via FR-mediated endocytosis, and loading doxorubicin (DOX) into AuCu-cys-FA (i.e., AuCu-cys-DOXFA) facilitated chemo-phototherapy because of photoresponsive anticancer drug release upon induction of hyperthermia.

Terminal Deoxynucleotidyl Transferase-Catalyzed Preparation of pH-Responsive DNA Nanocarriers for Tumor-Targeted Drug Delivery and Therapy.

Developing a highly efficient carrier for tumor-targeted delivery and site-specific release of anticancer drugs is a good way to overcome the side effects of traditional cancer chemotherapy. Benefiting from the nontoxic and biocompatible characteristics, DNA-based drug carriers have attracted increasing attention. Herein, we reported a novel and readily manipulated strategy to construct spherical DNA nanocarriers. In this strategy, terminal deoxynucleotidyl transferase (TdT)-catalyzed DNA extension reaction is used to prepare a thick DNA layer on a gold nanoparticle (AuNP) surface by extending long poly(C) sequences from DNA primers immobilized on AuNPs. The poly(C) extension products can then hybridize with G-rich oligonucleotides to give CG-rich DNA duplexes (for loading anticancer drug doxorubicin, Dox) and multiple AS1411 aptamers. Via synergic recognition of multiple aptamer units to nucleolin proteins, biomarker of malignant tumors, Dox-loaded DNA carrier can be efficiently internalized in cancer cells and achieve burst release of drugs in acidic organelles because of i-motif formation-induced DNA duplex destruction. An as-prepared pH-responsive drug carrier was demonstrated to be promising for highly efficient delivery of Dox and selective killing of cancer cells in both in vitro and in vivo experiments, thus showing a huge potential in anticancer therapy.

Thermal and Photo Dual-Responsive Core–Shell Polymeric Nanocarriers with Encapsulation of Upconversion Nanoparticles for Controlled Anticancer Drug Release

A thermal and photo dual-responsive drug delivery system is newly designed for controlled anticancer drug delivery. The concept of this design is to encapsulate upconversion nanoparticles in a phot...

Multifunctional Chitosan/Porous Silicon@Au Nanocomposite Hydrogels for Long-Term and Repeatedly Localized Combinatorial Therapy of Cancer via a Single Injection.

Considering the future clinical applications of localized cancer therapy, it is of great importance to construct injectable biodegradable nanocomposite hydrogels with combinatorial therapeutic efficacy. Here, porous silicon nanoparticles (PSiNPs) as host matrix were chosen to fabricate PSiNPs@Au nanocomposites via in situ reductive synthesis of gold nanoparticles. Then PSiNPs@Au nanocomposites were further incorporated into thermosensitive chitosan (CS) hydrogels to construct CS/PSiNPs@Au nanocomposite hydrogels, which showed in situ gelation at physiological temperature, excellent biodegradability, and biocompatibility. Especially with the encapsulation of CS hydrogels, PSiNPs@Au nanocomposites had a long-term stable photothermal effect with higher local temperature under near-infrared (NIR) laser irradiation, whether in vitro or in vivo. Besides, assisted by NIR laser irradiation, CS/PSiNPs@Au nanocomposite hydrogels exhibited a long-term sustained release of anticancer drugs (doxorubicin hydrochloride, DOX) in acidic tumor environments. Finally, DOX/CS/PSiNPs@Au precursors were administrated into tumor-bearing mice via a single intratumoral injection, which presented a significant synergistic chemo-photothermal therapeutic efficacy under repeated NIR laser irradiation during long-term cancer treatments. Accordingly, we developed a novel strategy to prepare multifunctional CS/PSiNPs@Au nanocomposite hydrogels and also demonstrated their potential applications in localized cancer therapy in future clinics.

Graphene oxide-based hydrogels as a nanocarrier for anticancer drug delivery

Graphene oxide (GO) possesses excellent mechanical strength, biocompatibility, colloidal stability, large surface area and high adsorption capability. It has driven to cancer nanotechnology to defeat cancer therapy obstacles, via integration into three-dimensional (3D) hydrogel network with biocompatible polymers as nanocomposites carrier, and controllable release of anticancer drugs. Specifically, the surface of GO affords π-π stacking and hydrophilic interactions with anticancer drugs. Additionally, modification of GO with various polymers such as natural and synthetic polymers enhances its biodegradability, drug loading, and target delivery. In this review, GO based hydrogels research accomplishments are reviewed on the aspects of crosslinking strategies, preparation methods, the model drug, polymer conjugation and modification with targeting ligands. Moreover, swelling kinetics, drug release profile and biological activity in vivo and in vitro are discussed. The biocompatibility of GO based hydrogels is also discussed from the perspective of its nano-bio interfaces. Apart from that, the clinical potential of GO based hydrogels and its major challenges are addressed in detail. Finally, this review concludes with a summary and invigorating future perspectives of GO based hydrogels for anticancer drug delivery. It is anticipated that this review can stimulate a new research gateway to facilitate the development of anticancer drug delivery by harnessing the unique properties of GO based hydrogels, such as large surface area, chemical purity, high loading capacity of drug, chemical stability, and the nature of lipophilic for cell membrane penetration.

Bicomponent nanofibrous scaffolds with dual release of anticancer drugs and biomacromolecules

Abstract

Polyaspartamide based hydrogel with cell recruitment properties for the local administration of hydrophobic anticancer drugs

By exploiting the chemical versatility and the high water dispersibility of α,β-poly(N-2-hydroxyethyl)D,L-aspartamide, in this work, two different polymer derivatives were synthesized for the first time. Obtained macromolecules were characterized and used to produce hydrogels exploitable for the local release of hydrophobic anticancer drugs. The first derivative, bearing pendant β-cyclodextrins, was employed to solubilize tamoxifen, chosen as a model drug, and to produce a water soluble supramolecular complex, as evidenced through tamoxifen phase solubility studies. The second derivative, bearing pendant Cyclo(Arginine-Glyicine-Asparagine-D-Phenilyalanine-Cysteine) peptide moieties, was used as a macromolecular crosslinker to obtain a hydrogel with cellular recruitment properties. The occurrence of crosslinking between the two derivatives was studied through rheological analysis and different procedures were employed to obtain tamoxifen medicated hydrogels. In vitro release studies, together with cytotoxicity and recruitment experiments, reveal that the obtained hydrogels can control the release of anticancer drugs, have a cytotoxic effect on human breast carcinoma cells and, thanks to the presence of adhesion moieties, are able to recruit cancer cells.

Selectively Oxidized Cellulose with Adjustable Molecular Weight for Controlled Release of Platinum Anticancer Drugs.

The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.

Advances in Therapeutic Implications of Inorganic Drug Delivery Nano-Platforms for Cancer.

Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites.

Tumor‐Microenvironment‐Induced Degradation of Ultrathin Gadolinium Oxide Nanoscrolls for Magnetic‐Resonance‐Imaging‐Monitored, Activatable Cancer Chemotherapy

The development of biodegradable inorganic nanoparticles with a tumor microenvironment-activated therapeutic mode of action is urgently needed for precision cancer medicine. Herein, the synthesis of ultrathin lanthanide nanoscrolls (Gd2 O3 NSs) is reported, which biodegrade upon encountering the tumor microenvironment. The Gd2 O3 NSs showed highly controlled magnetic properties, which enabled their high-resolution magnetic resonance imaging (MRI). Importantly, Gd2 O3 NSs degrade in a pH-responsive manner and selectively penetrate tumor tissue, enabling the targeted release of anti-cancer drugs. Gd2 O3 NSs can be efficiently loaded with an anti-cancer drug (DOX, 80 %) and significantly inhibit tumor growth with negligible cellular and tissue toxicity both in vitro and in vivo. This study may provide a novel strategy to design tumor microenvironment-responsive inorganic nanomaterials for biocompatible bioimaging and biodegradation-enhanced cancer therapy.

Abstract B040: Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy

Abstract An implantable anticancer device (IAD) that can eradicate local regional breast cancer recurrence (LRR), inhibit metastasis as well as to enhance the breast reconstruction during/after therapy is proposed. The IAD is developed by combining nanofiber-based chemo-photothermal therapy platform with check point blockade immunotherapy. Here we developed a coreshell electrospun nanofiber encapsulated with drug conjugated MoS2 as chemo-photothermal agent along with imiquimod as an immune response modifier. The near-infrared laser exposure to IADs can generate tumor-associated antigens from primary tumors, which in the presence of released imiquimod from IADs can show vaccine-like functions. Moreover, the nanofiber matrix will enable the sustained and tumor-specific anticancer drug release with a minimum initial burst release and the repeated photothermal capability to ensure the synergistic inhibition of tumor recurrence. In addition to that, the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) in combination with the generated immunologic responses will be able to attack remaining tumor cells causing metastasis inhibition with strong immunologic memory effect, which can shield against the tumor recurrence after the post elimination of initial tumors. The IAD nanofiber morphology resembles the extra cellular matrix (ECM) enrich the reconstruction of poor breast cosmesis resulted from the surgical treatment, by supporting the lipofilling of the surgical residual cavity to induce the adipogenic process. So, in this work we propose that the tumor associated antigens created in situ after photothermal therapy by the immune adjuvant nanofiber IAD could show vaccine-like functions, which in combination with checkpoint blockade show strong antitumor immune responses for effective cancer immunotherapy as a potential platform for synergistic inhibition of LRR and a great promise for the in situ breast reconstruction ability for better breast cosmesis. Citation Format: Afeesh Rajan Unnithan, Arathyram Ramachandra Kururp Sasikala, Chan Hee Park, Cheol Sang Kim. Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B040.

Self-assembled thixotropic silver cluster hydrogel for anticancer drug release

A biocompatible thixotropic hydrogel via photoreduction and self-assembly of silver clusters is described. This reaction avoids use of hydrogelators, crosslinkers or any exogenous toxic reducing agents, making it a facile and green method. Moreover, the formed ‘smart’ thixotropic hydrogel is pH-responsive and can encapsulate the hydrophobic anticancer drug doxorubicin hydrochloride (DOX). The thixotropic property allows it to be sol state, which can be injected directly into the site of breast tumors in mice; after removal of the shear stress, the sol reverts back to hydrogel, where it remains for delivery of DOX into cancerous cells. The DOX-loaded hydrogel presents remarkable inhibition efficacy towards tumor growth, in addition to reducing the organ toxicity.

Correction: In search of bioinspired hydrogels from amphiphilic peptides: a template for nanoparticle stabilization for the sustained release of anticancer drugs

Correction for ‘In search of bioinspired hydrogels from amphiphilic peptides: a template for nanoparticle stabilization for the sustained release of anticancer drugs’ by Radha Rani Mehra et al., New J. Chem., 2019, 43, 11666–11678.

Azo-based near-infrared fluorescent theranostic probe for tracking hypoxia-activated cancer chemotherapy in vivo.

A novel azo-based near-infrared fluorescent theranostic probe was synthesized, which is selectively activated under hypoxic conditions, resulting in the release of an active anticancer drug and a near-infrared fluorophore turn-on. Notably, the probe has been applied successfully to real-time visualization of drug delivery in 4T1, HepG2 cells, and mice.

Polyphosphazene-based nanocarriers for the release of agrochemicals and potential anticancer drugs.

The synthesis and characterisation of novel polyphosphazene nanocarriers, based on hydrophilic polyalkylene oxide Jeffamine M1000 and hydrophobic steroids with a glycinate linker for pH-controlled release of diosgenin and two brassinosteroids (DI31 and S7) with agrochemical and potential anticancer activity, is hereby described. Polyphosphazenes carrying approximately 17 wt% of DI31 or S7 self-assembled in water to form 120-150 nm nanoaggregates, which showed an excellent plant growth effect on radish cotyledons due to sustained delivery of approximately 30% of the agrochemicals after 4 days. Cytotoxic evaluation showed that all polymers carrying steroids and Jeffamine M1000 resulted in strong to moderate toxicity to MCF-7 cancer cells and were non-toxic to primary human lung fibroblast cells at 0.1 to 0.025 mg mL-1. Thus, DI31 and S7 bearing polymers applied at 10-4 to 10-6 mg mL-1 for delivery of recommended DI31 or S7 quantities to crops should be harmless to humans. Particularly, DI31 and S7 bearing polymers with strong cytotoxicity on MCF-7 and non-toxicity on primary human lung fibroblasts, good cell uptake after 6 hours, proper hydrodynamic sizes between 100 and 200 nm, and slow sustained release of cytotoxic drugs (DI31, S7) in acidic conditions might potentiate their accumulation in cancer tissues with good antitumour effects and minor side effects. These results demonstrated that preparation of brassinosteroid bearing polymers is a promising strategy for the preparation of better agrochemicals with reduced pollutant impact on sustainable agriculture and potential anticancer formulations based on analogues of brassinosteroids.

Mesoporous Silica Nanoparticles and Waste Derived-Siliceous Materials for Doxorubicin Adsorption and Release

Abstract Mesoporous silica nanoparticles (MSN) have been widely used for the drug delivery system due to their unique properties such as porous structure, high and tailorable internal and external surface area, as well as functionalizable surface. Due to the abundance of rice husk ash waste (RHA), extensive research had been conducted to convert these wastes to a useful resources. As RHA had been reported to contain high silica content (96.34%), it was seen as potential adsorbent as other silica materials. In this study, we have synthesized nano-silica materials from RHA (RHA-silica) to compare the potential of this waste-derived material with MSN for drug delivery application. RHA-silica was applied to the adsorption and release of model anti-cancer drugs, doxorubicin, and the performance was compared with the synthesized mesoporous silica nanoparticles (MSN). The characterization of the material was also compared and it was observed that the adsorption of doxorubicin was 65% on RHA-silica and MSN was 79.5% and 90.8%, while the total release percentage was 30.7% and 48.8%, respectively. From the result, it is expected that the waste-derived silica material could be further modified and optimized for the drug delivery application, as well as the appropriate modification and functionalization to suite the need for adsorption and release of drugs, but with lower cost and significant contribution to a greener chemistry.

Multistage rocket: integrational design of a prodrug-based siRNA delivery system with sequential release for enhanced antitumor efficacy.

An integrated peptide-camptothecin prodrug (RSC) system was designed as a nano-sized multistage rocket for the efficient complexation and controlled sequential release of siRNA and anticancer drug under tumor-relevant reductive and esterase-enriched conditions, which facilitated the avoidance of negative interactions and maximized the synergistic effect.

Gadolinium-containing polymer microspheres: a dual-functional theranostic agent for magnetic resonance imaging and cancer therapy

Preparation of poly(gadolinium methacrylate-co-methacrylic acid) copolymer microspheres with high MRI contrast efficiency and controlled anti-cancer drug loading and release capability.

In search of bioinspired hydrogels from amphiphilic peptides: a template for nanoparticle stabilization for the sustained release of anticancer drugs

This report presents the efficiency of palmitic acid-based proteolytically stable, biocompatible hydrogelators for the sustained release of anticancer drugs.