Release Of Drug Doxorubicin Research Articles

Two-Dimensional Biodegradable l-Cysteine-Iodine Nanosheets for Computed Tomography-Guided Cancer Synergistic Sonodynamic Therapy and Chemotherapy.

Biodegradable versatile inorganic nanomaterials are highly desirable in the field of nanomedicine. Here, for the first time, we report a kind of novel two-dimensional biodegradable l-cysteine-iodine (l-Cys-I) nanosheet with high computed tomography (CT) imaging ability and sonosensitization efficacy. Such l-Cys-I nanosheets consist of iodine molecules and l-Cys, where the iodine molecules are coordinated and stabilized by l-Cys and cross-linked to form nanosheets through disulfide bonds. The large and convenient functional surface is further modified with targeting moieties DSPE-PEG-RGD and cancer drug doxorubicin (DOX) to construct a nanotheranostic nanoplatform (CIRD). Under ultrasound irradiation, the CIRD nanosheets assist in tremendous reactive oxygen species generation and controllable DOX release, leading to remarkable anticancer performance both in vitro and in vivo due to the synergistic sonodynamic therapy (SDT) and chemotherapy. Our results validate that the CIRD nanosheets enable effective body excretion and negligible systemic toxicity owing to the biodegradation properties. The CIRD nanosheets, with biodegradability, biocompatibility, and versatility, hold great promise in nanotheranostics.

High loading and sustained-release system of doxorubicin-carbon dots as nanocarriers for cancer therapeutics

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%.In vitrodrug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

PH-Responsive supramolecular vesicles for imaging-guided drug delivery: Harnessing aggregation-induced emission.

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt, TBTQ-C 6 , acts as the host component (H) forming host-guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives, G1 and G2, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells in vitro. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.

Nanocarrier-based drug delivery system with dual targeting and NIR/pH response for synergistic treatment of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.

Preparation of environmentally responsive PDA&DOX@LAC live drug carrier for synergistic tumor therapy

The development of intelligent, environmentally responsive and biocompatible photothermal system holds significant importance for the photothermal combined therapy of tumors. In this study, inspired by Lactobacillus (LAC), we prepared a biomimetic nanoplatform PDA&DOX@LAC for tumor photothermal-chemotherapy by integrating the chemotherapeutic drug doxorubicin (DOX) with dopamine through oxidative polymerization to form polydopamine (PDA) on the surface of LAC. The PDA&DOX@LAC nanoplatform not only achieves precise and controlled release of DOX based on the slightly acidic microenvironment of tumor tissues, but also exhibits enzyme-like properties to alleviate tumor hypoxia. Under near-infrared light irradiation, it effectively induces photothermal ablation of tumor cells, enhances cellular uptake of DOX with increasing temperature, and thus efficiently inhibits tumor cell growth. Moreover, it is further confirmed in vivo experiments that photothermal therapy combined with PDA&DOX@LAC induces tumor cells apoptosis, releases tumor-associated antigens, which is engulfed by dendritic cells to activate cytotoxic T lymphocytes, thereby effectively suppressing tumor growth and prolonging the survival period of 4T1 tumor-bearing mice. Therefore, the PDA&DOX@LAC nanoplatform holds immense potential in precise tumor targeting as well as photothermal combined therapy and provides valuable insights and theoretical foundations for the development of novel tumor treatment strategies based on endogenous substances within the body.

Polymer Nanoparticles for Preferential Delivery of Drugs Only by Exploiting the Slightly Elevated Temperature of Cancer Cells and Real-Time Monitoring of Drug Release.

Rapid proliferation and a faster rate of glycolysis in cancer cells often result in an elevated local temperature (40-43 °C) at the tumor site. Nanoparticles prepared from polymers with two lower critical solution temperatures (LCSTs) can be utilized to take advantage of this subtle temperature elevation to deliver anticancer drugs preferably to the cancer cells, thereby enhancing the overall therapeutic efficacy and reducing side effects. In this direction, we synthesized N-vinyl-2-pyrrolidone (NVP) and substituted NVP (sub-NVP: C2-NVP, C4-NVP)-based polymers with precisely controlled LCSTs by varying the ratio of NVP and sub-NVP. The first LCST (LCST1) was kept below 37 °C to promote self-assembly, drug loading, and structural stability in physiological conditions and the second LCST (LCST2) was in the range of 40-43 °C to ensure mild hyperthermia-induced drug release. Additionally, covalent attachment of tetraphenylethylene (TPE, AIEgen) resulted in aggregation-induced emission in thermoresponsive micellar nanoparticles in which TPE acted as a Förster Resonance Energy Transfer (FRET) pair with the loaded anticancer drug doxorubicin (DOX). Tracking of FRET-induced fluorescence recovery of TPE molecules was utilized to confirm the real-time thermoresponsive release of DOX from nanoparticles and eventual localization of TPE in the cytoplasm and DOX in the nucleus. In vitro cellular studies such as cytotoxicity, cellular uptake, and thermoresponsive drug release showed that the DOX-loaded polymeric nanoparticles were nontoxic to normal cells (HEK-293) but significantly more effective in cancer cells (MCF-7) at 40 °C. To our knowledge, this is the first report of preferential delivery of anticancer drugs only by exploiting the slightly elevated temperature of cancer cells.

Tumor Growth Inhibition and Induced the Immunogenic Death of Tumor Cells in Prostate Tumor Bone Metastases by Photothermal Therapy Mediated with Au Nanoparticles Modified with PDA

AbstractUpon progression to the metastatic stage, prostate tumors commonly exhibit multi‐drug resistance. Combining multiple treatment protocols can be beneficial in overcoming this resistance, which is often attributed to tumor heterogeneity. Recently, nano‐photosensitizer‐mediated photothermal therapy is shown to inhibit tumor growth through multiple pathways, including thermal ablation and activation of the antitumor immune response. In this study, gold nanoparticles (Au) are selected as the core photosensitizer. Then, the photothermal conversion of Au is augmented through dopamine coating, and the chemotherapy drug doxorubicin (DOX) is grafted to the dopamine coating. The release of DOX from DOX‐loaded dopamine‐modified gold nanoparticles (Au@PDA@DOX) occurred in response to an acidic environment. The combination of chemotherapy and thermal ablation better inhibits the growth, migration, and invasion of tumor cells and induced tumor cell apoptosis and necrosis in vitro. More importantly, thermal ablation induces the immunogenic death of prostate tumor cells (RM‐1) cells. The transition of prostate tumors from a “cold” to a “hot” tumor with immunogenicity is observed. The combination effectively activates the antitumor immune response, inhibits tumor growth, and alleviated bone damage by tumors in vivo. It is indicated that Au@PDA@DOX nanoparticles will offer a novel treatment protocol for prostate tumor bone metastases.

Cytotoxic Effects of Doxorubicin on Cancer Cells and Macrophages Depend Differently on the Microcarrier Structure.

Microparticles are versatile carriers for controlled drug delivery in personalized, targeted therapy of various diseases, including cancer. The tumor microenvironment contains different infiltrating cells, including immune cells, which can affect the efficacy of antitumor drugs. Here, prototype microparticle-based systems for the delivery of the antitumor drug doxorubicin (DOX) were developed, and their cytotoxic effects on human epidermoid carcinoma cells and macrophages derived from human leukemia monocytic cells were compared in vitro. DOX-containing calcium carbonate microparticles with or without a protective polyelectrolyte shell and polyelectrolyte microcapsules of about 2.4-2.5 μm in size were obtained through coprecipitation and spontaneous loading. All the microstructures exhibited a prolonged release of DOX. An estimation of the cytotoxicity of the DOX-containing microstructures showed that the encapsulation of DOX decreased its toxicity to macrophages and delayed the cytotoxic effect against tumor cells. The DOX-containing calcium carbonate microparticles with a protective polyelectrolyte shell were more toxic to the cancer cells than DOX-containing polyelectrolyte microcapsules, whereas, for the macrophages, the microcapsules were most toxic. It is concluded that DOX-containing core/shell microparticles with an eight-layer polyelectrolyte shell are optimal drug microcarriers due to their low toxicity to immune cells, even upon prolonged incubation, and strong delayed cytotoxicity against tumor cells.

PH and temperature dual-responsive hollow mesoporous silica nanoparticles for drug encapsulation and delivery

In this work, pH and temperature dual-responsive drug delivery vehicles (CDs/PNVCL@HMSNs) with 57.05% drug loading efficiency were prepared. Hollow mesoporous silicon nanoparticles (HMSNs) were synthesized by selective etching. The mixed shells on the surface of HMSNs were composed of carbon dots (CDs) and poly (N-vinylcaprolactam) (PNVCL), which were linked to HMSNs via Schiff base reaction. At room environment (pH = 7.4, T = 25 °C), PNVCL was stretched, so that the model drug Doxorubicin (DOX) could be transported freely through the mesopores. In the blood stream (pH = 7.4, T = 37 °C), PNVCL was collapsed, and DOX was encapsulated to form PNVCL@HMSNs-DOX. CDs were grafted to give CDs/PNVCL@HMSNs-DOX and could further inhibit the leakage of drugs. At the acidic environment of the tumor site, Schiff base bonds broke, leading to shell shedding and DOX release. The drug release could be real-time monitored by the change in fluorescence intensity, which was confirmed by the linear fitting of the fluorescence strength of CDs and the percentage of DOX released. CDs/PNVCL@HMSNs are intriguing drug delivery systems (DDSs), which can combine real-time monitoring and control of drug release.

Fe3O4-Incorporated Metal-Organic Framework for Chemo/Ferroptosis Synergistic Anti-Tumor via the Enhanced Chemodynamic Therapy.

Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, an enhanced chemodynamic anti-tumor therapy strategy by promoting the Fenton reaction by using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe3O4 as a therapeutic platform is proposed. Carboxymethyl cellulose (CMC) is used as a stabilizer of Fe3O4, which is then decorated on the surface of ZIF-8 via the electrostatic interaction and serves as an efficient Fenton reaction trigger. Meanwhile, the pH-responsive ZIF-8 scaffold acts as a container to encapsulate the chemotherapeutic drug doxorubicin (DOX). The obtained DOX-ZIF-8@Fe3O4/CMC (DZFC) nanoparticles concomitantly accelerate DOX release and generate more hydroxyl radicals by targeting the lysosomes in cancer cells. In vitro and in vivo studies verify that the DZFC nanoparticles trigger glutathione peroxidase 4 (GPX4)-dependent ferroptosis via the activation of the c-Jun N-terminal kinases (JNK) signaling pathway, following to achieve the chemo/ferroptosis synergistic anti-tumor efficacy. No marked toxic effects are detected during DZFC treatment in a tumor-bearing mouse model. This composite nanoparticle remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theragnostic nanomedicines.

Sodium Chloride Induced pH and Temperature Responsive Biocompatible Hydrogel of Choline Oleate for Transdermal Drug Delivery of Doxorubicin

AbstractNanodrug carriers have various biological and pharmaceutical applications, and among all the transdermal drug delivery is fascinating, specifically for localized medication therapy to a specific diseased organ or limited diseased area of the body, such as breast cancer cells or carcinoma cells. This way the efficacy of drug can be enhanced and its side effect to other healthy organs can be reduced to great extent. To ameliorate the limitations of traditional polymeric drug delivery systems, such as limited quantity and heterogeneity of the loaded drug, we developed a NaCl induced biocompatible gel of wormlike micelles of surface active ionic liquid (SAIL) i. e. choline oleate ([Ch][Ol]). Apart from the pH and temperature responsive mechanical properties, the designed gel also show good skin permeability, biocompatibility, adhesive qualities, stretchability, and viscoelasticity. The gel was tested for encapsulation of anticancer drug doxorubicin (DOX) and its transdermal delivery at pH=7.4 and pH=5.2. This system exhibits tremendous transdermal permeability of DOX and selective release more amount of the drug at 5.2 pH. Hence for localised and targeted delivery of an anticancer drug, this system can be proven to be suitable.

An ATP-responsive ZIF-based NIR fluorescence nanosystem for enhanced chemo-photodynamic therapy of tumors.

The combination of chemotherapy and photodynamic therapy holds immense potential for achieving synergistic anti-tumor efficacy. However, challenges such as poor stability and premature drug release prior to reaching tumor sites impede the widespread application of this synergistic therapeutic approach. In this study, a novel ATP-responsive NIR fluorescence nanosystem (CDZ) for imaging-guided chemotherapy and PDT has been developed. This nanosystem, based on ZIF-90, encapsulates the chemotherapy drug doxorubicin (DOX) and the photosensitizer asymmetrical cyanine dye Cy through self-assembly. The obtained nanosystem CDZ could efficiently avoid premature drug leakage in the blood circulation due to its high stability in the physiological environment and accumulates at the tumor sites via the enhanced permeability and retention (EPR) effect. Upon uptake by tumor cells, the skeleton structure of CDZ is disrupted by overexpressed ATP levels, leading to the release of DOX, which inhibits cancer cell proliferation and induces cell death. Additionally, the released photosensitizer Cy emits strong NIR fluorescence signals, enabling real-time imaging of ATP levels in tumors. Moreover, under NIR light irradiation, this nanosystem generates high levels of ROS, achieving effective phototherapy even in deeper tumor regions. In tumor model mice, CDZ demonstrated a high rate of tumor inhibition without causing damage to major organs. This ZIF-based NIR fluorescence nanosystem, combining chemotherapy and photodynamic therapy, holds promise as a solution for treating and monitoring cancer without the associated risks of resistance and systemic toxicity.

Synthesis, characterization and anticancer effect of doxorubicin-loaded dual stimuli-responsive smart nanopolymers.

Nanopolymers represent a significant group of delivery vehicles for hydrophobic drugs. In particular, dual stimuli-responsive smart polymer nanomaterials might be extremely useful for drug delivery and release. We analyzed the possibility to include the known antitumor drug doxorubicin (DOX), which has antimitotic and antiproliferative effects, in a nanopolymer complex. Thus, doxorubicin-loaded temperature- and pH-sensitive smart nanopolymers (DOX-SNPs) were produced. Characterizations of the synthesized nanostructures were carried out including zeta potential measurements, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The loading capacity of the nanopolymers for DOX was investigated, and encapsulation and release studies were carried out. In a final step, the cytotoxicity of the DOX-nanopolymer complexes against the HeLa cancer cell line at different concentrations and incubation times was studied. The DOX release depended on temperature and pH value of the release medium, with the highest release at pH 6.0 and 41 °C. This effect was similar to that observed for the commercial liposomal formulation of doxorubicin Doxil. The obtained results demonstrated that smart nanopolymers can be efficiently used to create new types of doxorubicin-based drugs.

Enhancing antitumor immunity with stimulus-responsive mesoporous silicon in combination with chemotherapy and photothermal therapy.

Due to the immunosuppressive tumor microenvironment (TME) and potential systemic toxicity, chemotherapy often fails to elicit satisfactory anti-tumor responses, so how to activate anti-tumor immunity to improve the therapeutic efficacy remains a challenging problem. Photothermal therapy (PTT) serves as a promising approach to activate anti-tumor immunity by inducing the release of tumor neoantigens in situ. In this study, we designed tetrasulfide bonded mesoporous silicon nanoparticles (MSNs) loaded with the traditional drug doxorubicin (DOX) inside and modified their outer layer with polydopamine (DOX/MSN-4S@PDA) for comprehensive anti-tumor studies in vivo and in vitro. The MSN core contains GSH-sensitive tetrasulfide bonds that enhance DOX release while generating hydrogen sulfide (H2S) to improve the therapeutic efficacy of DOX. The polydopamine (PDA) coating confers acid sensitivity and mild photothermal properties upon exposure to near-infrared (NIR) light, while the addition of hyaluronic acid (HA) to the outermost layer enables targeted delivery to CD44-expressing tumor cells, thereby enhancing drug accumulation at the tumor site and reducing toxic side effects. Our studies demonstrate that DOX/MSN@PDA-HA can reverse the immunosuppressive tumor microenvironment in vivo, inducing potent immunogenic cell death (ICD) of tumor cells and improving anti-tumor efficacy. In addition, DOX/MSN@PDA-HA significantly suppresses tumor metastasis to the lung and liver. In summary, DOX/MSN@PDA-HA exhibits controlled drug release, excellent biocompatibility, and remarkable tumor inhibition capabilities through synergistic chemical/photothermal combined therapy.

Nanocatalytic theranostics with intracellular mutual promotion for ferroptosis and chemo-photothermal therapy

The reactive oxygen species (ROS) produced through the Fenton reaction, induces lipid peroxide (LPO), causing cellular structural damage and ultimately triggering ferroptosis. However, the generation of ROS in the tumor microenvironment (TME) is limited by the catalytic efficiency of the Fenton reaction. Herein, a novel hollow mesoporous silica nanoparticle (HMSN) combined with multi-metal sulfide-doped mesoporous silica nanocatalyzers (NCs) was developed, namely MxSy-HMSN NCs (M represents Cu Mn and Fe, S denotes sulfur). The MxSy-HMSN can dramatically enhanced the ferroptosis by: (1) facilitating the conversion of H2O2 to ·OH through Fenton or Fenton-like reactions through co-catalysis; (2) weakening ROS scavenging systems by depleting the over expressed glutathione (GSH) in TME; (3) providing exceptional photothermal therapy to augment ferroptosis. The MxSy-HMSN can also act as smart cargos for anticancer drug-doxorubicin (DOX). The release of DOX is responsive to GSH/pH/Near-infrared Light (NIR) irradiation at the tumor lesion, significantly improving therapeutic outcomes while minimizing side effects. Additionally, the MxSy-HMSN has demonstrated excellent magnetic resonance imaging (MRI) potential. This smart MxSy-HMSN offer a synergetic approach combining ferroptosis with chemo-photothermal therapy and magnetic resonance imaging (MRI) diagnose, which could be an informative guideline for the design of future NCs.

Hydrophobicity-Adaptive Polymers Trigger Fission of Tumor-Cell-Derived Microparticles for Enhanced Anticancer Drug Delivery.

Tumor-cell-derived microparticles (MPs) can function as anticancer drug-delivery carriers. However, short blood circulation time, large-size-induced insufficient tumor accumulation and penetration into tumor parenchyma, as well as limited cellular internalization by tumor cells and cancer stem cells (CSCs), and difficult intracellular drug release restrict the anticancer activity of tumor-cell-derived MP-based drug-delivery systems. In this work, hydrophobicity-adaptive polymers based on poly(N-isopropylacrylamide) are anchored to tumor-cell-derived MPs for enhanced delivery of the anticancer drug doxorubicin (DOX). The polymers are hydrophilic in blood to prolong the circulation time of DOX-loaded MPs (DOX@MPs), while rapidly switching to hydrophobic at the tumor acidic microenvironment. The hydrophobicity of polymers drives the fission of tumor-cell-derived MPs to form small vesicles, facilitating tumor accumulation, deep tumor penetration, and efficient internalization of DOX@MPs into tumor cells and CSCs. Subsequently, the hydrophobicity of polymers in acidic lysosomes further promotes DOX release to nuclei for strong cytotoxicity against tumor cells and CSCs. The work provides a facile and simple strategy for improved anticancer drug delivery of tumor-cell-derived MPs.

Wood structure-inspired injectable lignin-based nanogels as blood-vessel-embolic sustained drug-releasing stent for interventional therapies on liver cancer

An embolic reagent with easy injection, well-controlled target embolization, and sustained release of chemotherapy drugs is urgently needed for successful trans-arterial chemo-embolization (TACE) treatment. However, the development of a highly effective embolic reagent is still challenged. Here, inspired and guided by the structural supporting properties and defense mechanisms of wood cell walls, an ideal lignin-based embolic nanogel (DOX-pN-KL) was explored. Based on the mechanical support of branched lignin and the π-π stacking force between the lignin aromatic ring with anti-tumor drug doxorubicin (DOX), DOX-pN-KL showed the highest mechanical strength among the reported thermosensitive embolization nanogel and performed high drug-loading and favorable sustained-release. Moreover, further TACE treatment and tumor microenvironment evaluation of VX2 tumor-bearing rabbits showed that this nanogel can completely block all levels of vessels in long term and continuously release DOX, thus having effective inhibition on tumor growth and metastasis. DOX-pN-KL is expected to be a promising alternative reagent for interventional therapy.

A self-monitoring microneedle patch for light-controlled synergistic treatment of melanoma.

Melanoma is the most aggressive and malignant form of skin cancer. Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release. Here, a self-monitoring microneedle (MN)-based drug delivery system, which integrates a dissolving MN patch with aggregation-induced emission (AIE)-active PATC microparticles, is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma. The PATC polymeric particles, termed D/I@PATC, encapsulate both of chemotherapeutic drug doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon light illumination, PATC gradually dissociates into smaller particles, causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles, thereby not only enabling direct observation of the drug release process under light stimuli, but also facilitating verification of drug release by fluorescence recovery after light trigger. Moreover, encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo. In a tumor-bearing mouse, the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited ∼97% melanoma inhibition rate without inducing any evident systemic toxicity, suggesting a great potential for skin cancer treatment in clinics.

Light and pH responsive catanionic vesicles based on a chalcone/flavylium photoswitch for smart drug delivery: From molecular design to the controlled release of doxorubicin

Spatially and temporally localized delivery is a promising strategy to circumvent adverse effects of traditional drug therapy such as drug toxicity and prolonged treatments. Stimuli-responsive colloidal nanocarriers can be crucial to attain such goals. Here, we develop a delivery system based on dual light and pH responsive vesicles having a cationic bis-quat gemini surfactant, 12–2-12, and a negatively charged amphiphilic chalcone, C4SCh. The premise is to exploit the chalcone/flavylium interconversion to elicit a morphological change of the vesicles leading to the controlled release of an encapsulated drug. First, the phase behavior of the catanionic system is studied and the desirable composition yielding stable unilamellar vesicles identified and selected for further studies. The solutions containing vesicles (Dh ≈ 200 nm, ζ-potential ≈ 80 mV) are in-depth characterized by light microscopy, cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and surface tension measurements. Upon subjecting the vesicles to UV irradiation (λ = 365 nm) at near neutral pH (≈ 6.0), no morphological effects are observed, yet when irradiation is coupled with pH = 3.0, the majority of the vesicles are disrupted into bilayer fragments. The anticancer drug doxorubicin (DOX) is successfully entrapped in the non-irradiated vesicles, yielding an encapsulation efficiency of ≈ 25% and a loading capacity of ≈ 3%. The release profile of the drug-loaded vesicles is then studied in vitro in four conditions: i) no stimuli (pH = 6.0); ii) irradiation, pH = 6.0; iii) no irradiation and adjusted pH = 3.0; iv) irradiation and adjusted pH = 3.0 Crucially, irradiation at pH = 3.0 leads to a sustained release of DOX to ca. 80% (within 4 h), whereas cases i) and ii) lead to only ≈ 25 % release and case iii) to 50% release but precipitation of the vesicles. Thus, our initial hypothesis is confirmed: we present a proof of concept delivery system where light and pH act as inputs of an AND logic gate mechanism for the controlled release of a relevant biomedical drug (output). This may prove useful if the irradiated nanocarriers meet acidified physiological environments such as tumors sites, endosomes or lysosomes.