Triggered Drug Release Research Articles

Nested Nanobubbles for Ultrasound-Triggered Drug Release.

Because of their size (1–10 μm), microbubble-based drug delivery agents suffer from confinement to the vasculature, limiting tumor penetration and potentially reducing the drug efficacy. Nanobubbles (NBs) have emerged as promising candidates for ultrasound-triggered drug delivery because of their small size, allowing drug delivery complexes to take advantage of the enhanced permeability and retention effect. In this study, we describe a simple method for production of nested-nanobubbles (Nested-NBs) by encapsulation of NBs (∼100 nm) within drug-loaded liposomes. This method combines the efficient and well-established drug-loading capabilities of liposomes while utilizing NBs as an acoustic trigger for drug release. Encapsulation was characterized using transmission electron microscopy with an encapsulation efficiency of 22 ± 2%. Nested-NBs demonstrated echogenicity using diagnostic B-mode imaging, and acoustic emissions were monitored during high-intensity focused ultrasound (HIFU) in addition to monitoring of model drug release. Results showed that although the encapsulated NBs were destroyed by pulsed HIFU [peak negative pressure (PNP) 1.54–4.83 MPa], signified by loss of echogenicity and detection of inertial cavitation, no model drug release was observed. Changing modality to continuous wave (CW) HIFU produced release across a range of PNPs (2.01–3.90 MPa), likely because of a synergistic effect of mechanical and increased thermal stimuli. Because of this, we predict that our NBs contain a mixed population of both gaseous and liquid core particles, which upon CW HIFU undergo rapid phase conversion, triggering liposomal drug release. This hypothesis was investigated using previously described models to predict the existence of droplets and their phase change potential and the ability of this phase change to induce liposomal drug release.

From Anatomy to Functional and Molecular Biomarker Imaging and Therapy: Ultrasound Is Safe, Ultrafast, Portable, and Inexpensive.

Ultrasound is the most widely used medical imaging modality worldwide. It is abundant, extremely safe, portable, and inexpensive. In this review, we consider some of the current development trends for ultrasound imaging, which build upon its current strength and the popularity it experiences among medical imaging professional users.Ultrasound has rapidly expanded beyond traditional radiology departments and cardiology practices. Computing power and data processing capabilities of commonly available electronics put ultrasound systems in a lab coat pocket or on a user's mobile phone. Taking advantage of new contributions and discoveries in ultrasound physics, signal processing algorithms, and electronics, the performance of ultrasound systems and transducers have progressed in terms of them becoming smaller, with higher imaging performance, and having lower cost. Ultrasound operates in real time, now at ultrafast speeds; kilohertz frame rates are already achieved by many systems.Ultrasound has progressed beyond anatomical imaging and monitoring blood flow in large vessels. With clinical approval of ultrasound contrast agents (gas-filled microbubbles) that are administered in the bloodstream, tissue perfusion studies are now routine. Through the use of modern ultrasound pulse sequences, individual microbubbles, with subpicogram mass, can be detected and observed in real time, many centimeters deep in the body. Ultrasound imaging has broken the wavelength barrier; by tracking positions of microbubbles within the vasculature, superresolution imaging has been made possible. Ultrasound can now trace the smallest vessels and capillaries, and obtain blood velocity data in those vessels.Molecular ultrasound imaging has now moved closer to clinic; the use of microbubbles with a specific affinity to endothelial biomarkers allows selective accumulation and retention of ultrasound contrast in the areas of ischemic injury, inflammation, or neoangiogenesis. This will aid in noninvasive molecular imaging and may provide additional help with real-time guidance of biopsy, surgery, and ablation procedures.The ultrasound field can be tightly focused inside the body, many centimeters deep, with millimeter precision, and ablate lesions by energy deposition, with thermal or mechanical bioeffects. Some of such treatments are already in clinical use, with more indications progressing through the clinical trial stage. In conjunction with intravascular microbubbles, focused ultrasound can be used for tissue-specific drug delivery; localized triggered release of sequestered drugs from particles in the bloodstream may take time to get to clinic. A combination of intravascular microbubbles with circulating drug and low-power ultrasound allows transient opening of vascular endothelial barriers, including blood-brain barrier; this approach has reached clinical trial stage. Therefore, the drugs that normally would not be getting to the target tissue in the brain will now have an opportunity to produce therapeutic efficacy.Overall, medical ultrasound is developing at a brisk rate, even in an environment where other imaging modalities are also advancing rapidly and may be considered more lucrative. With all the current advances that we discuss, and many more to come, ultrasound may help solve many problems that modern medicine is facing.

LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

Combination therapy such as photothermal therapy (PTT) enhanced chemotherapy is regarded as a promising strategy for cancer treatment. Herein, we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL. To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance, the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics: doxorubicin (DOX) and paclitaxel (PTX). Besides, indocyanine green (ICG) was encapsulated, and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles. The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content, trigger drug release in responsive to the reductive environment, realize high cellular uptake via dual peptides and laser irradiation, and achieve higher cytotoxicity via chemo-photothermal combination therapy. Hence, the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

Synergistic performance of triggered drug release and photothermal therapy of MCF7 cells based on laser activated PEGylated GO + DOX

Graphene oxide is used as a singular 2D nano-carrier in cancer therapy. Here, graphene oxide is used as a hybrid chemo-drug graphene oxide (GO) + doxorubicin (DOX), mainly due to its unique chemical and optical properties. The laser triggers GO + DOX for selective drug delivery to optimize the drug release. The characterization of GO is investigated in terms of laser properties at 808 nm. Furthermore, the laser activates GO + DOX compounds to treat MCF7 cancerous cells. The drug release strongly depends on the temperature rise that mainly effects on the viability of the cancerous cells of interest. DOX simultaneously acts as a chemo-drug and as an optical fluorescent agent, whereas GO performs as an efficient photothermal nano-carrier. In fact, the GO-DOX hybrid drug demonstrates multifunctional during malignant cell treatment. We have shown that the laser heating of GO enhances the release percentage up to a treatment yield of 90%. This arises from the synergistic nature of DOX and GO compounds in simultaneous chemo/photo thermal therapy. Furthermore, the fluorescence property of DOX is used to assess the GO uptake using confocal microscope imaging.

Engineered exosome for NIR-triggered drug delivery and superior synergistic chemo-phototherapy in a glioma model

Most of chemotherapies are less effective when using alone. Exosomes (Exos) are cell derived nanovesicles that can serve as delivery nanoplatforms. Thus, Exos-based synergistic treatment is emerging as a promising strategy. Nevertheless, it is unknown about the underlying mechanism of Exos-based synergistic chemo-phototherapy at the gene level, especially in a glioma model. Here, we demonstrate that the combined therapy leads a superior chemo-phototherapy effect compared with chemotherapy or phototherapy alone. With the aid of Exos, the encapsulated agents can circulate for a longer time in vivo and effectively accumulated at tumor site. The local hyperthermia induced under near-infrared irradiation (NIR), impacts the permeability of Exos membrane and triggers drug release for maintaining a sustained chemotherapeutic efficacy. More importantly, the possible molecular mechanisms of Exos-based synergistic chemo-phototherapy are found to be involved in specific pathways including apoptosis, self-renewal repression and EMT program reversion. These data indicate that the engineered Exos can effectively combine chemotherapy and phototherapy to advance treatment of glioma and applied to other cancers as well, provide a new therapeutic strategy and potential molecular targets for clinical treatment.

CRGD mediated redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for efficiently intracellular antitumor drug delivery

To improve antitumor efficiency of chemotherapy and reduce side effect, according to the physiological characteristics of tumor tissues and tumor intracellular microenvironment, a multifunctional drug delivery system with properties of long circulation, active targeting, redox and pH triggered drug release was established based on the Generation 4 polyamidoamine dendrimer (PAMAM). First, the redox cleavable disulfide bonds (SS) were introduced for linking polyethylene glycol (PEG) with PAMAM to form PAMAM-S-S-PEG (PSSP). Then cRGD peptide was applied to the PEG end of PSSP to construct RGD-PSSP conjugates. Finally, encapsulating the antitumor chemotherapy drug doxorubicin (DOX) into the hydrophobic cavity of RGD-PSSP conjugates constructed the RGD-PSSP/DOX drug delivery system. The in vitro experiments displayed that RGD-PSSP/DOX NPs showed obviously redox and pH dual sensitive drug release profile. MTT and cell uptake observation elucidated cRGD modification could increase the cytotoxicity, and promote the uptake of B16 cells and HUVEC cells both overexpressing integrin ανβ3on cell membrane. Cell uptake mechanism investigation further revealed that RGD-PSSP/DOX interacted with plasma membrane via specific recognition of cRGD peptide with integrin ανβ3, and was subsequently internalized mainly through clathrin- and caveolin-mediated endocytosis. Remarkably, RGD-PSSP/DOX presented superior anticancer activity and lower heart and kidney toxicity in vivo, which could be regarded as a potential candidate for efficient antitumor chemotherapy drug delivery.

Surface engineering of magnetic nanoparticles for hyperthermia and drug delivery

AbstractMagnetic nanoparticles (MNP) have emerged as a relevant material for biomedical applications based on drug delivery systems and magnetic hyperthermia. When carefully tailored, their surface properties can enhance the solubility, bioavailability, permeability, metabolism, excretion, cell internalization and recognition of many medicines, which are parameters highly desired when one think in the development and efficiency increasing of several therapies. Allied to it, an interesting synergism can be achieved by the use of magnetic fields as trigger of drug release from thermosensitive polymer‐modified MNP or as a tool to increase accumulation of medicine in specific site. Faced it, here it shows how surface engineering of MNP can improve its biomedical relevance due to enhancement of cellular recognition, biocompatibility and drug release of several medicines. Furthermore, particular attention will be paid to the use of magnetic hyperthermia, which has acted synergic to improve MNP effects of many drug delivery systems.

Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models

Hepatocellular carcinoma (HCC) has become the fourth predominant cause of cancer-related deaths worldwide, and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resistance and great toxic effects. Triptolide (TP), a key ingredient from the traditional Chinese medical herb, has been utilized to treat inflammation and antitumor for centuries. However, investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades. Herein, we reported the development of a reduction-responsive drug delivery system loaded with TP for glutathione (GSH)-triggered drug release for cancer therapy. With the GSH-sensitive TP loaded nanoparticles, the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated, which is likely due to sustained stepwise release of active TP within cancer cells. Moreover, in a patient-derived tumor xenograft model of liver cancer, administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP. These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment.

Metal-Organic Framework Composites for Theragnostics and Drug Delivery Applications.

Among a plethora of nano-sized therapeutics, metal-organic frameworks (MOFs) have been some of the most investigated novel materials for, predominantly, cancer drug delivery applications. Due to their large drug uptake capacities and slow-release mechanisms, MOFs are desirable drug delivery vehicles that protect and transport sensitive drug molecules to target sites. The inclusion of other guest materials into MOFs to make MOF-composite materials has added further functionality, from externally triggered drug release to improved pharmacokinetics and diagnostic aids. MOF-composites are synthetically versatile and can include examples such as magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that improve the blood-circulation time. From synthesis to applications, this review will consider the main developments in MOF-composite chemistry for biomedical applications and demonstrate the potential of these novel agents in nanomedicine. It is concluded that, although vast synthetic progress has been made in the field, it requires now to develop more biomedical expertise with a focus on rational model selection, a major comparative toxicity study, and advanced targeting techniques.

Chitosan-Gated Fluorescent Mesoporous Silica Nanocarriers for the Real-Time Monitoring of Drug Release.

We have constructed a novel gated nanocarrier for the real-time monitoring of drug release, consisting of three parts: (i) mesoporous silica nanoparticles (MSNs) as the drug carrier, (ii) chitosan as the nanovalve to block and unlock the pores, and (iii) 1,8-naphthalimide fluorophore as a connecting arm and fluorescent signal source. In the absence of glutathione (GSH), the integrity of the system results in the formation of pores in a closed state and the sulfone would block the intramolecular charge transfer (ICT) process, leading to no fluorescence emission. However, the nucleophilic attack of GSH can cause the removal of the chitosan and recovery of ICT property, thus triggering drug release and green fluorescence emission. The results demonstrate that the change of GSH concentration in vivo or vitro would lead to a change in drug release as well as a concurrent change in fluorescence signal, which can expand the application of our gated nanocarrier for monitoring different drug release in real time.

Smart gold nanocages for mild heat-triggered drug release and breaking chemoresistance

Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed. Here, we designed a smart nanosystem of thermo-sensitive liposome coated gold nanocages with doxorubicin (DOX) loading (LAD) for near-infrared (NIR)-triggered drug release and chemo-photothermal combination therapy. The biocompatible liposomes coating facilitated the cellular uptake of LAD and meanwhile avoided drug leakage during the circulation. More importantly, LAD exhibited controllable photothermal conversion property and produced mild heat under NIR irradiation, which not only triggered DOX release and transferred DOX from lysosome to nucleus, but also elicited the mild heat cell killing effect to improve the curative efficiency. Further mechanism study revealed that mild heat could reverse drug resistance by down-regulation of the chemoresistance-related markers (e.g., HSF-1, p53, P-gp), and inhibited DOX export and increased drug sensitiveness, thereby prominently increased the anticancer efficiency. This versatile nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release and combination tumor therapy.

Paclitaxel/IR1061-Co-Loaded Protein Nanoparticle for Tumor-Targeted and pH/NIR-II-Triggered Synergistic Photothermal-Chemotherapy.

PurposeThe aim of this study was to develop an “all-in-one” nanoplatform that integrates at the second near-infrared (NIR-II) region dye IR1061 and anticancer drug paclitaxel (PTX) into an apoferritin (AFN) nanocage (IR-AFN@PTX). Simultaneously, folic acid (FA), tumor target molecule, was conjugated onto IR-AFN@PTX to be IR-AFN@PTX-FA for tumor-targeted and pH/NIR-II-triggered synergistic photothermal-chemotherapy.MethodsIR1061 was firstly reacted with PEG and then conjugated with AFN to be IR-AFN. Then, FA was conjugated onto the surface of IR-AFN to be IR-AFN-FA. At last, PTX was incorporated into IR-AFN-FA to fabricate a nanoplatform IR-AFN@PTX-FA. The NIR-II photothermal properties and pH/NIR-II triggered drug release were evaluated. The ability of IR-AFN@PTX-FA to target tumors was estimated using optical bioluminescence. In vitro and in vivo synergistic therapeutic effects of pH/NIR-II-triggered and tumor-targeted photothermal-chemotherapy were investigated in 4T1 tumor model.ResultsIR-AFN@PTX-FA showed excellent water solubility and physiological stability, which significantly enhanced the solubility of both IR1061 and PTX. After 5 min of laser irradiation at 1064 nm, IR-AFN@PTX-FA exhibited an effective photothermal effect compared with laser irradiation at 808 nm, even when blocked with 0.6 cm thick chicken breast. Cellular uptake experiments showed IR-AFN@PTX-FA utilized clathrin-mediated and caveolae-mediated endocytosis pathways to enter 4T1 cells, and was then delivered by the endosome to the lysosome. NIR-II laser irradiation and pH could synergistically trigger PTX release, inducing significant tumor inhibition in vitro and in vivo.ConclusionAs a novel “all-in-one” nanoplatform, IR-AFN@PTX-FA was found to selectively target tumors and showed very efficient NIR-II photothermal effects and pH/NIR-II triggered drug release effects, showing a remarkable, synergistic photothermal-chemotherapy effect.

Surface Modification of Liposomes Using IR700 Enables Efficient Controlled Contents Release Triggered by Near-IR Light.

Stimuli-responsive liposomes are promising drug carriers for cancer treatment because they enable controlled drug release and the maintenance of desired drug concentrations in tumor tissue. In particular, near-IR (NIR) light is a useful stimulus for triggering drug release from liposomes based on its advantages such as deep tissue penetration and safety. Previously, we found that a silicon phthalocyanine derivative, IR700, conjugated to antibodies, can induce the rupture of the cell membrane following irradiation by NIR light. Based on this finding, we constructed IR700-modified liposomes (IR700 liposomes) and evaluated their drug release properties triggered by NIR light. IR700 liposomes released substantial amounts of encapsulated calcein following irradiation by NIR light. Drug release was substantially suppressed by the addition of sodium azide, suggesting that liposomal membrane permeabilization was mediated by singlet oxygen generated from IR700. Moreover, calcein release from IR700 liposomes triggered by NIR light was promoted under conditions of deoxygenation and the presence of electron donors. Thus, membrane disruption should be induced by the physical change of IR700 from highly hydrophilic to hydrophobic as we previously described, although singlet oxygen can cause a certain level of membrane disruption under normoxia. We also observed that doxorubicin-encapsulated IR700 liposomes exhibited significant cytotoxic effects against CT-26 murine colon carcinoma cells following NIR light exposure. These results indicate that IR700 liposomes can efficiently release anti-cancer drugs following NIR light irradiation even under hypoxic conditions and, therefore, they would be useful for cancer treatment.

Sonochemical fabrication of magnetic reduction-responsive alginate-based microcapsules for drug delivery

The magnetic reduction-responsive alginate-based microcapsules (MRAMCs) have been developed successfully with thiolated alginate and oleic acid (OA) modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) via a facile sonochemical method. The obtained MRAMCs could be used as multifunctional carriers for hydrophobic drugs targeted delivery and triggered release due to their merits, such as biocompatibility, non-immunogenicity, magnetic targeting drug delivery and reduction-responsive drug release. The MRAMCs were endowed with magnetic targeting function owing to the encapsulation of the superparamagnetic OA-Fe3O4 NPs, which was confirmed by transmission electron microscope and vibrating sample magnetometer. In addition, the MRAMCs presented excellent reduction-responsive release ability for hydrophobic drugs on account of the disulfide bonds in the wall of microcapsules, which were formed by the cross-linking of sulfhydryl groups on thiolated alginate under ulstrasonication. Meanwhile, confocal laser scanning microscopy measurement indicated that coumarin 6 acted as a hydrophobic model drug could be loaded into MRAMCs easily by dissolving in soybean oil before ultrasonication. Overall, these results demonstrated that MRAMCs would be a promising platform to build controllable drug delivery systems for targeted delivery and triggered release of hydrophobic drugs in biomedical application.

Switchable Lipid Provides pH-Sensitive Properties to Lipid and Hybrid Polymer/Lipid Membranes.

Blending amphiphilic copolymers and lipids constitutes a novel approach to combine the advantages of polymersomes and liposomes into a new single hybrid membrane. Efforts have been made to design stimuli-responsive vesicles, in which the membrane’s dynamic is modulated by specific triggers. In this investigation, we proposed the design of pH-responsive hybrid vesicles formulated with poly(dimethylsiloxane)-block-poly(ethylene oxide) backbone (PDMS36-b-PEO23) and cationic switchable lipid (CSL). The latter undergoes a pH-triggered conformational change and induces membrane destabilization. Using confocal imaging and DLS measurements, we interrogated the structural changes in CSL-doped lipid and hybrid polymer/lipid unilamellar vesicles at the micro- and nanometric scale, respectively. Both switchable giant unilamellar lipid vesicles (GUV) and hybrid polymer/lipid unilamellar vesicles (GHUV) presented dynamic morphological changes, including protrusions and fission upon acidification. At the submicron scale, scattered intensity decreased for both switchable large unilamellar vesicles (LUV) and hybrid vesicles (LHUV) under acidic pH. Finally, monitoring the fluorescence leakage of encapsulated calcein, we attested that CSL increased the permeability of GUV and GHUV in a pH-specific fashion. Altogether, these results show that switchable lipids provide a pH-sensitive behavior to hybrid polymer/lipid vesicles that could be exploited for the triggered release of drugs, cell biomimicry studies, or as bioinspired micro/nanoreactors.

Customized hybrid and NIR-light triggered thermoresponsive drug delivery microparticles synthetized by photopolymerization in a one-step flow focusing continuous microreactor

Photopolymerization is a selective technique that takes advantage of light-sensitive molecules to initiate and propagate monomeric structures to render covalently bonded macromolecular materials structures known as polymers. Herein, we present a novel one-step microfluidic synthesis of customized hybrid-thermoresponsive Poly(N-isopropylacrylamide) (PNIPAm) based microparticles (MPs) containing plasmonic hollow gold nanoparticles (HGNPs) and bupivacaine (BVP) used as a model drug. Those hybrid microparticles were prepared using a flow-focusing microreactor coupled to a UV LED device built with a simple outer PTFE tubing and an inner flexible capillary. Different tubing characteristics and flow rate ratios were altered in order to control the size of the resulting microparticles. In addition, components such as monomer, crosslinker and photoinitiator concentrations, as well as LED intensity and irradiation time were tuned to obtain different MPs and their characteristics and polymerization rates were compared by Gel Permeation Chromatography (GPC). Thermoresponsive properties were analyzed and the presence of HGNPs was confirmed in light-activated triggered drug release applications. Bupivacaine loading and release studies were evaluated with the resulting hollow and solid microparticles (which were obtained depending on the polymerization rate used) and their temperature responsiveness was assessed using a NIR laser when HGNPs were present in the constructs. Finally, cytotoxicity studies, cell-cycle arrest and apoptotic induction were carried out to certify their suitability for further biomedical applications to be used as triggerable drug depots.

Applications of Micro/Nanotechnology in Ultrasound-based Drug Delivery and Therapy for Tumor.

Ultrasound has been broadly used in biomedicine for both tumor diagnosis as well as therapy. The applications of recent developments in micro/nanotechnology promote the development of ultrasound-based biomedicine, especially in the field of ultrasound-based drug delivery and tumor therapy. Ultrasound can activate nano-sized drug delivery systems by different mechanisms for ultrasound- triggered on-demand drug release targeted only at the tumor sites. Ultrasound Targeted Microbubble Destruction (UTMD) technology can not only increase the permeability of vasculature and cell membrane via sonoporation effect but also achieve in situ conversion of microbubbles into nanoparticles to promote cellular uptake and therapeutic efficacy. Furthermore, High Intensity Focused Ultrasound (HIFU), or Sonodynamic Therapy (SDT), is considered to be one of the most promising and representative non-invasive treatment for cancer. However, their application in the treatment process is still limited due to their critical treatment efficiency issues. Fortunately, recently developed micro/nanotechnology offer an opportunity to solve these problems, thus improving the therapeutic effect of cancer. This review summarizes and discusses the recent developments in the design of micro- and nano- materials for ultrasound-based biomedicine applications.

Development of Novel Magnetoliposomes Containing Nickel Ferrite Nanoparticles Covered with Gold for Applications in Thermotherapy

Multifunctional nanosystems combining magnetic and plasmonic properties are a promising approach for cancer therapy, allowing magnetic guidance and a local temperature increase. This capability can provide a triggered drug release and synergistic cytotoxic effect in cancer cells. In this work, nickel ferrite/gold nanoparticles were developed, including nickel ferrite magnetic nanoparticles decorated with plasmonic gold nanoparticles and core/shell nanostructures (with a nickel ferrite core and a gold shell). These nanoparticles were covered with a surfactant/lipid bilayer, originating liposome-like structures with diameters below 160 nm. The heating capacity of these systems, upon excitation with light above 600 nm wavelength, was assessed through the emission quenching of rhodamine B located in the lipid layer. The developed nanosystems show promising results for future applications in thermotherapy.

The Effects of Photosensitized Lipid Oxidation on Supported Lipid Bilayer Formation and Membrane Deformation

Lipid oxidation by reactive oxygen species (ROS) has a number of negative consequences in biology. Additionally, photosensitized lipid oxidation has been explored as a way to trigger drug release from liposomal containers. In this work we explore the effects of photosensitized lipid oxidation on the interactions of phospholipid vesicles with SiO2 surfaces. Using quartz crystal microbalance with dissipation monitoring (QCM-D), we determined that light exposure radically alters the pathway of supported lipid bilayer (SLB) formation for vesicles that contain lipid-conjugated fluorophores. Instead of the well-established two-step adsorption-rupture pathway, vesicles that have undergone photosensitized peroxidation rupture immediately upon encountering the SiO2 surface. The alteration of the vesicle rupture pathway seems to be dependent on the molecular position of the fluorescent moiety. Vesicles containing phospholipids with a BODIPY fluorophore conjugated to their fatty acid tails show the most pronounced effects. On the other hand, vesicles containing lipids with NBD conjugated to their head or tail groups show negligible differences compared to controls. We also show that antioxidants such as alpha-tocopherol (vitamin E) can attenuate the effects of photo peroxidation on the rupture pathway. Fluorescence microscopy was also used to observe lipid oxidation of a SLB, the effects of which cause membrane defects, namely membrane tubulation followed by vesiculation. Image analysis has been used to probe the characteristics of these defects, including the length of the tubes, the diameter of the subsequent vesicles, and the rate of growth of each. A direct correlation has been observed between tube length and vesicle diameter, and that the rate of growth for tubulation and vesiculation slows over time.

Self-assembled pH-responsive polymeric nanoparticles based on lignin-histidine conjugate with small particle size for efficient delivery of anti-tumor drugs

As a natural biomaterial, lignin is mainly obtained from waste in the pulping and papermaking industry, and is becoming an alternative to petroleum-based chemicals. Lignin-based nanoparticles provide new possibilities for value-added utilization. In this work, a novel pH-responsive drug-loaded polymeric nanoparticle platform based on aminated lignin-histidine conjugate and 10-hydroxycamptothecin, AL-His/HCPT NP, is prepared by self-assembly. Based on the acidic microenvironment of tumor cells (endosomes: pH ∼5–6; lysosomes: pH ∼4–5), the AL-His/HCPT NPs are successfully imparted the pH-responsiveness by histidine, a pH-responsive small molecule to achieve triggered drug release. After 19 h of simulated release in vitro, the drug release amount of the nanoparticles was 39.1 % at pH 7.2, 63.1 % at pH 5.5, and 72.5 % at pH 4.5, indicating the pH-responsiveness. Meanwhile, the NPs have relatively small particle size (∼40 nm), which is key to anti-tumor nano-carriers. It is characterized by great biocompatibility, good drug loading performance (∼15.57 wt%), and effective cellular uptake (∼2 times that of pure HCPT). In 4T1 tumor-bearing mice model, the group treated with NPs shows excellent anti-tumor effect (tumor growth inhibition rate: ∼2 times that of pure HCPT) and reduced side effects. These results indicate that AL-His/HCPT NPs have great application prospects in drug delivery.