Triggered Drug Release Research Articles

CRGD-targeted gold-based nanoparticles overcome EGFR-TKI resistance of NSCLC via low-temperature photothermal therapy combined with sonodynamic therapy.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a first-line targeted drug for the treatment of advanced non-small cell lung cancer (NSCLC) in clinical practice, but EGFR-TKI-acquired resistance limits its therapeutic effect. To address this challenge, a novel multifunctional gold-based targeted nanoparticle-based drug delivery system is fabricated. The gold-based nanoparticle is loaded with the EGFR-TKI (gefitinib) and IR780, and the surface-modified gold nanoshell layer has a photothermal effect for thermally triggered drug release. Finally, the unique binding of cyclic arginine-glycine-aspartic acid (cRGD) to the αvβ3 receptor ensured that the nanoparticle (cRGD-GIPG) targeted transport into drug-resistant NSCLC cells was functional. Due to the sonodynamic properties of IR780, ultrasound (US) irradiation promoted reactive oxygen species (ROS) generation, while low-temperature photothermal therapy (PTT) not only promoted the release of drug, but also further enhanced the cytotoxic effects of ROS. In turn, it blocked the activation of TGF-β/PDLIM5/SMAD resistance pathway and induced apoptosis of drug-resistant cells through mitochondrial apoptosis, enabling the treatment of EGFR-TKI-resistant NSCLC. The low-temperature PTT combined with sonodynamic therapy (SDT) by cRGD-GIPG thus shows potent anticancer activity against EGFR-TKI-resistant NSCLC cells in vitro and in vivo. The present work provides a valuable strategy for highly targeted and EGFR-TKI-resistant reversal therapy in NSCLC.

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

A novel multifunctional carrier with magnetic-NIR luminescent-microwave heating characteristics for drug delivery

We constructed a novel core–shell structured Fe3O4@WO3-x(x = 0∼1)@GdF3: Yb/Er nanoparticles with magnetic-NIR luminescent-microwave heating characteristics used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug doxorubicin (DOX). The porous surface of Fe3O4@WO3-x(x = 0∼1)@GdF3:Yb/Er nanoparticles can store DOX molecules by means of physical adsorption. The Fe3O4 core and GdF3: Yb/Er shell functioned successfully for magnetic targeting (1.40 emu•g−1) and NIR fluorescence imaging (NIR 650–850 nm), respectively. The introduction of WO3-x(x = 0∼1) with LSPR effect enhanced the luminescence of near-infrared region of Fe3O4@WO3-x(x = 0∼1)@GdF3:Yb/Er nanoparticles successfully. In addition, the WO3-x(x = 0∼1) acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the DOX release of 12% under microwave irradiation for 10 s outclass the 2% within 1 h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. Moreover, it can monitor the drug release process in real time under the guidance of near infrared imaging, which is convenient to evaluate the therapeutic effect. This work provides a new idea for realizing the visual real-time dynamic monitoring of the chemotherapy process and realizing “positioning-timing-quantitative” administration, thus improving the chemotherapy effect.

One-step fabrication of multiphasic Janus microparticles with programmed degradation properties based on a microfluidic chip

This work aimed to develop a multiphasic Janus particle system for programmed drug delivery. A phase separation based one-step microfluidic preparation process was demonstrated to generate triple-phase Janus microparticles with different degradation properties in each phase. In this system, particles with a series of complicated structures were generated, and programmed degradation behaviors according to the structures were achieved. Partial degradation of the particles and cargo release triggered by change of ambient temperature or pH could be realized as well. Further, graphene nanosheets and silica nanospheres were modified in the microparticles by using the principle of Pickering emulsion to enrich the functions of the particles. To reveal the potential of the particles in drug delivery applications, doxorubicin and curcumin were co-loaded in triple-phase microparticles, and zonal drug loading was achieved. In vitro drug release profiles and tumor cell apoptosis study indicated that the particles provided programmed release behavior as well as enhanced tumor inhibition efficacy compared with free drug administration and monophasic particles. This study proposed a facile and one-step fabrication method of multiphasic particles possessing programmed and triggered drug release kinetics, and may be the first attempt to generate triple-phase particles with phase separation method in a droplet microfluidic chip.

Tablet formulation with dual control concept for efficient colonic drug delivery

Aim of this study was to develop a tablet formulation for targeted colonic drug release by implementing two control mechanisms: A pH-sensitive coating layer based on Eudragit® FS 30 D to prevent drug release in the upper gastrointestinal tract, combined with a matrix based on plant-derived polysaccharide xyloglucan to inhibit drug release after coating removal in the small intestine and to allow microbiome triggered drug release in the colon. In vitro dissolution tests simulated the passage through the entire gastrointestinal tract with a four-stage protocol, including microbial xyloglucanase addition in physiologically relevant concentrations as microbiome surrogate to the colonic dissolution medium. Matrix erosion was monitored in parallel to drug release by measurement of reducing sugar equivalents resulting from xyloglucan hydrolysis. Limited drug release in gastric and small intestinal test stages and predominant release in the colonic stage was achieved. The xyloglucan matrix controlled drug release after dissolution of the enteric coating through the formation of a gummy polysaccharide layer at the tablet surface. Matrix degradation was dependent on enzyme concentration in the colonic medium and significantly accelerated drug release resulting in erosion-controlled release process. Drug release at physiologically relevant enzyme concentration was completed within the bounds of colonic transit time. The dual control concept was applicable to two drug substances with different solubility, providing similar release rates in colonic environment containing xyloglucanase. Drug solubility mechanistically affected release, with diffusion of caffeine, but not of 5-ASA, contributing to the overall release rate out of the matrix tablet.

Construction of MOFs nanoplatform with pH-triggered release of protocatechuic acid for intervertebral disc degeneration therapy

Lower back pain is a significant contributor to disability and incapacity in adults. Up to 40 % of lower back pain is considered to be caused primarily by disc degeneration. The pH value in the intervertebral disc (IVD) usually decreases with the progression of degeneration, which can act as an initiator to trigger the release of drugs precisely for inhibiting the intervertebral disc degeneration (IDD). Herein, we fabricated a pH-responsive metal organic framework (MOF) to load anti-inflammatory protocatechuic acid (PCA), followed by the encapsulation of hyaluronic acid (HA), the final product was abbreviated as MOF@PH. The results showed that the acidic microenvironment could trigger drug release from MOF@PH featured by an increasing release proportion with pH decreasing. The cell assessment indicated that MOF@PH could suppress the inflammatory response of the nucleus pulposus significantly, downregulate the expression of related inflammatory markers (IL-6, ROS, NLRP-3 etc.) and promote the expression of nucleus pulposus specific markers. The administration of MOF@PH in rat disc degeneration model was proven able to effectively delay the degeneration process. The pH-sensitive MOF@PH may offer an effective strategy to precisely treat the IDD with desired therapeutic effects.

A nanodiamond chemotherapeutic folate receptor-targeting prodrug with triggerable drug release

Cancer chemotherapy is often accompanied by severe off-target effects that both damage quality of life and can decrease therapeutic compliance. This could be minimized through selective delivery of cytotoxic agents directly to the cancer cells. This would decrease the drug dose, consequently minimizing side effects and cost. With this goal in mind, a dual-gated folate-functionalized nanodiamond drug delivery system (NPFSSD) for doxorubicin with activatable fluorescence and cytotoxicity has been prepared. Both the cytotoxic activity and the fluorescence of doxorubicin (DOX) are quenched when it is covalently immobilized on the nanodiamond. The NPFSSD is preferentially uptaken by cancer cells overexpressing the folate receptor. Then, once inside a cell, the drug is preferentially released within tumor cells due to their high levels of endogenous of glutathione, required for releasing DOX through cleavage of a disulfide linker. Interestingly, once free DOX is loaded onto the nanodiamond, it can also evade resistance mechanisms that use protein pumps to remove drugs from the cytoplasm. This nanodrug, used in an in vivo model with local injection of drugs, effectively inhibits tumor growth with fewer side effects than direct injection of free DOX, providing a potentially powerful platform to improve therapeutic outcomes.

Enhanced Nuclear Accumulation of Doxorubicin Delivered by pH-Triggered Polydopamine-Shelled Mesoporous Silica for Chemo-Photothermal Therapy.

Adequate delivery of therapeutic agents to their intended molecular targets is crucial in tumor therapy. Versatile drug carriers need to overcome the challenges coming from the systemic circulation, membrane barriers, and endo-lysosomal degradation. Herein, hyaluronic acid-conjugated polydopamine (HA-PDA)-shelled mesoporous silica nanoparticles encapsulated with doxorubicin (MSNs-DOX) were successfully fabricated for targeted tumor therapy. Compared with reported studies focusing on the pH-sensitive release in tumors, we especially revealed the significant role of lysosomal release in DOX nuclear accumulation. After active targeting and CD44-mediated endocytosis in tumor cells, the PDA layer of the nanoparticles would be peeled off to trigger drug release owing to MSNs gatekeeper in acidic lysosomes. Subsequently, DOX molecules passively diffused into nuclei. The intracellular DOX transportation was evidenced by DOX accumulation in nuclei, lysosomal location of nanoparticles, and lysosome acidification inhibition test. After discharging of the cargoes from nanoparticles, PDA shells from residual nanoparticles were able to produce localized hyperthermia under NIR irradiation entrapped in lysosomes, inducing synergistic chemo-photothermal effect. Under NIR treatment, HA-PDA@MSNs-DOX presented a prominent tumor inhibition rate without obvious side effects. This study indicated the potent nuclear delivery and synergetic chemo-photothermal therapy achieved by HA-PDA-shelled MSNs.

Redox-Sensitive multifunctional hyaluronic acid-based nanomicelles with Fine-controlled anticancer drug release

A significant contributor to cancer-related death globally is metastatic breast cancer. To reduce death rates, tumor-specific penetration and triggered drug release are crucial. Herein, targeted intracellular doxorubicin (Dox) delivery system was effectively prepared based on redox-sensitive hyaluronic acid-palmitoyl (HA-ss-PA) copolymers. The amphiphilic copolymers self-assembled into nano and showed outstanding drug-loading capacities and encapsulation efficiency for Dox. Micelles were stable under physiological conditions, but they quickly disintegrated in the presence of a reducing agent. The intracellular location of the fluorescent probe rhodamine b demonstrated that HA-ss-PA micelles are an efficient approach for drug delivery in breast cancer cells. Based on flow cytometry and live/dead assay, observations indicated that micelles induce apoptosis in both MCF-7 and MDA-MB-231 cells. In vivo evaluation in tumor-bearing mice confirmed that HA-ss-PA micelles exhibited excellent tumor-targeting activity. These findings imply that redox-sensitive HA-ss-PA micelles are promising candidates for use as intracellular delivery systems for hydrophobic anti-cancer drugs.

Microrobot with Gyroid Surface and Gold Nanostar for High Drug Loading and Near-Infrared-Triggered Chemo-Photothermal Therapy.

The use of untethered microrobots for precise synergistic anticancer drug delivery and controlled release has attracted attention over the past decade. A high surface area of the microrobot is desirable to achieve greater therapeutic effect by increasing the drug load. Therefore, various nano- or microporous microrobot structures have been developed to load more drugs. However, as most porous structures are not interconnected deep inside, the drug-loading efficiency may be reduced. Here, we propose a magnetically guided helical microrobot with a Gyroid surface for high drug-loading efficiency and precise drug delivery. All spaces inside the proposed microrobot are interconnected, thereby enabling drug loading deep inside the structure. Moreover, we introduce gold nanostars on the microrobot structure for near-infrared-induced photothermal therapy and triggering drug release. The results of this study encourage further exploration of a high loading efficiency in cell-based therapeutics, such as stem cells or immune cells, for microrobot-based drug-delivery systems.

Mesoporous silica nanoparticle core-shell matrix (MSN CSM) engineered by green approach for pH triggered release of anticancer drugs

The present work exhibits an alternative route to design a nano-carrier using simple electrostatic interactions of biopolymeric layers on Mesoporous Silica Nanoparticle surface using Layer by Layer (LbL) technique. The doxorubicin (DOX) loaded MSN nano-carrier is coated with positively charged chitosan followed by a coating of negatively charged sodium carboxymethyl cellulose (Na-CMC) to form a DOX-loaded MSN Core-Shell Matrix (DOX-MSN CSM). The prepared MSN nano-carrier exhibits a high encapsulation efficiency of DOX (∼93 %) due to its porous nature (∼832 m2/gm) and negative surface charge (-21.5 mV). It exhibits a controlled release of DOX (∼21 %) at physiological pH (7.4 pH) and improved drug release (∼67 %) at cancer cells pH (5.4 pH) after 48 h. Further, the in-vitro cell line study using MDA-MB 231 cells reconfirms the slower and controlled release of DOX from the engineered DOX-MSN CSM. The confocal microscopy result shows that the DOX is internalized via endocytosis into the nucleus of the cells. The cell viability assay confirms more cells viable (∼76 %) for DOX-MSN CSM than free DOX (∼49 %) at the end of 24 h. The present study shows an alternate route to the conventional complex multi-step processes such as coupling reactions or chemical crosslinkers involving solvents. The proposed MSN core–shell matrix can be a potential nano-carrier for cancer drug delivery.

Triggered drug release of surface cyclic peptide gatekeepers with endothelial cell targeting sequence conjugated to mesoporous nanocontainers

• The sequence targeting tumor endothelial cell is introduced to the peptide gatekeeper. • The release of entrapped drugs is completely inhibited in the absence of stimuli. • The structure of peptide gatekeeper was converted by addition of bioreductant. • The entrapped drugs in nanocontainers are released on-demand. Peptides have been used to develop drug delivery vehicles because of their ability to selectively target desired cells and respond to various biomolecules. In this study, a WIFPWIQL sequence with the capability of selectively targeting angiogenic endothelial cells was introduced to prepare a cyclized peptide gatekeeper on the surface of mesoporous silica nanocontainers (MSNs). In the absence of any stimulus, the WIFPWIQL-containing peptide gatekeeper, cyclized by a cystine unit, inhibited the release of drugs encapsulated within the MSNs. In the presence of a bioreductant, the disulfide bond of the cystine unit was decomposed to yield thiol units, and the peptide gatekeeper was converted into a linear structure. The encapsulated drugs in the MSNs were released responsively.

Gold-Nanoparticle Hybrid Nanostructures for Multimodal Cancer Therapy.

With the urgent need for bio-nanomaterials to improve the currently available cancer treatments, gold nanoparticle (GNP) hybrid nanostructures are rapidly rising as promising multimodal candidates for cancer therapy. Gold nanoparticles (GNPs) have been hybridized with several nanocarriers, including liposomes and polymers, to achieve chemotherapy, photothermal therapy, radiotherapy, and imaging using a single composite. The GNP nanohybrids used for targeted chemotherapy can be designed to respond to external stimuli such as heat or internal stimuli such as intratumoral pH. Despite their promise for multimodal cancer therapy, there are currently no reviews summarizing the current status of GNP nanohybrid use for cancer theragnostics. Therefore, this review fulfills this gap in the literature by providing a critical analysis of the data available on the use of GNP nanohybrids for cancer treatment with a specific focus on synergistic approaches (i.e., triggered drug release, photothermal therapy, and radiotherapy). It also highlights some of the challenges that hinder the clinical translation of GNP hybrid nanostructures from bench to bedside. Future studies that could expedite the clinical progress of GNPs, as well as the future possibility of improving GNP nanohybrids for cancer theragnostics, are also summarized.

Clickable Polymer Ligand-Functionalized Iron Oxide Nanocubes: A Promising Nanoplatform for 'Local Hot Spots' Magnetically Triggered Drug Release.

Exploiting the local heat on the surface of magnetic nanoparticles (MNPs) upon exposure to an alternating magnetic field (AMF) to cleave thermal labile bonds represents an interesting approach in the context of remotely triggered drug delivery. Here, taking advantages of a simple and scalable two-step ligand exchange reaction, we have prepared iron oxide nanocubes (IONCs) functionalized with a novel multifunctional polymer ligand having multiple catechol moieties, furfuryl pendants, and polyethylene glycol (PEG) side chains. Catechol groups ensure a strong binding of the polymer ligands to the IONCs surface, while the PEG chains provide good colloidal stability to the polymer-coated IONCs. More importantly, furfuryl pendants on the polymer enable to click the molecules of interest (either maleimide-fluorescein or maleimide-doxorubicin) via a thermal labile Diels-Alder adduct. The resulting IONCs functionalized with a fluorescein/doxorubicin-conjugated polymer ligand exhibit good colloidal stability in buffer saline and serum solution along with outstanding heating performance in aqueous solution or even in viscous media (81% glycerol/water) when exposed to the AMF of clinical use. The release of conjugated bioactive molecules such as fluorescein and doxorubicin could be boosted by applying AMF conditions of clinical use (16 kAm-1 and 110 kHz). It is remarkable that the magnetic hyperthermia-mediated release of the dye/drug falls in the concentration range 1.0-5.0 μM at an IONCs dose as low as 0.5 gFe/L and at no macroscopical temperature change. This local release effect makes this magnetic nanoplatform a potential tool for drug delivery with remote magnetic hyperthermia actuation and with a dose-independent action of MNPs.

Magneto-Mechanically Triggered Thick Films for Drug Delivery Micropumps.

Given the demanding use of controlled drug delivery systems, our attention was focused on developing a magnetic film that can be triggered in the presence of a magnetic field for both drug delivery and the actuating mechanism in micropump biomedical microelectromechanical systems (BioMEMS). Magnetic alginate films were fabricated in three steps: the co-precipitation of iron salts in an alkaline environment to obtain magnetite nanoparticles (Fe3O4), the mixing of the obtained nanoparticles with a sodium alginate solution containing glycerol as a plasticizer and folic acid as an active substance, and finally the casting of the final solution in a Petri dish followed by cross-linking with calcium chloride solution. Magnetite nanoparticles were incorporated in the alginate matrix because of the well-established biocompatibility of both materials, a property that would make the film convenient for implantable BioMEMS devices. The obtained film was analyzed in terms of its magnetic, structural, and morphological properties. To demonstrate the hypothesis that the magnetic field can be used to trigger drug release from the films, we studied the release profile in an aqueous medium (pH = 8) using a NdFeB magnet as a triggering factor.

Size-transformable gelatin/nanochitosan/doxorubicin nanoparticles with sequentially triggered drug release for anticancer therapy

The translation of nanoparticles in cancer treatment is limited by their low drug-loading capacity, poor colloidal stability, insufficient tumor penetration, and uncontrolled drug release. Herein, gelatin/nanochitosan/doxorubicin nanoparticles (GND) are developed by crosslinking nanochitosan (NCT) with gelatin for doxorubicin delivery. The hydrophilicity and stability properties of GND allow it to be protected and have a long circulation time in blood. The GND formulation exhibited shedding and triggered release effects as well as improved colloidal stability. When reaching the tumor site, matrix metallopeptidase-2 (MMP-2) from the tumor environment degrades gelatin from 178-nm GND to release smaller 4 nm nanochitosan/doxorubicin (ND) nanoparticles for deep tumor penetration and efficient tumor cell endocytosis. Following endocytosis by tumor cells, the intracellular low pH and MMP-2 further trigger doxorubicin release, resulting in superior inhibitory capacity against cancer cells. Using a mouse tumor-bearing model, the superior anticancer activity and good in vivo biocompatibility of GND were verified. The rational design of tumor-penetrating GND enables MMP-2/pH sequentially triggered intelligent drug delivery, providing a practical approach for anticancer therapy.

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience.

At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.

Smart Bandage to Monitor Combat Wounds and Control Bacterial Infections During Military Operations

In the United States Army, nearly 50% of soldiers experience 1 or more injuries a year during deployment and mission operations. The most common injuries during these operations can be classified between saturable wounds, such as lacerations and punctures, and non-saturable wounds, such as blast wounds, gunshot wounds, head injuries, bone fractures, burns, and ulcers. In all cases, the leading post-wound treatment are complications associated with wound infections; with sepsis being the leading cause of death in after wound care. Gram-positive, gram-negative, and fungal infections are the most prevalent types of infections seen in the U.S. Army, with Staphylococcus aureus (s. aureus) being the most common infection recorded in about 20% of soldiers. Present techniques are limited to using pressure pads and antibacterial gels for preventing infections. These approaches cannot be integrated into a wearable construct and do not offer a reliable method of management. Therefore, monitoring and treating infection in combat wounds is a major healthcare challenge in wound care management for army application.Our work focuses on developing a wearable smart bandage that can detect a change in pH and lactate using an electrochemical sensing approach that responds as a function of bacterial infection and can monitor in real-time using data generated by sensors. Further, the pH sensing causes a triggered release of drug molecules that control bacterial infection in the wound bed. The electrochemical pH sensors were fabricated by printing commercial flexible inks onto a stretchable thermoplastic polyurethane (TPU, TE-11C DuPontTM) film, and subsequently heat laminating over a cotton gauze (thickness: 100 μm). A conventional three-electrode cell assembly consisting of SPCE, Ag/AgCl as a reference electrode, and a Pt wire as a counter electrode was used for the experiments. CV was performed to assess the performance of the electrodeposited polyaniline. The measurements were performed at a scan rate of 0.02 V s-1 in a potential window of 1 V and -0.2 V. Sensor stability was characterized under room temperature and physiological conditions (RT) over 3 days. In case of the triggered drug release, we synthesized chitosan-pH responsive polymer using an ionic gelation process and drug ampicillin and kanamycin were encapsulated with a 64% efficiency. The polymer released drug above pH 6.5 which correlated to 105 bacterial CFU/ml, thus was incorporated in the bandage matrix and served as a controlled release when infection occurs. It was observed that pH tends to rise as infection progress therefore ideal for drug release in an alkaline environment.Finally, the sensor was able to detect bacterial cells ranging from 102-105 cells and the drug release showed an 82% reduction in cell number. The work carried out highlights an integrated sensor to sense bacterial infections and simultaneously trigger drug release. In light of current findings, this study allowed us to understand the dynamic interaction occurring between the sensor surface and wound bed and the sensor data showed a direct correlation to bacterial infection. The sensor can be integrated into a multiplex wearable device detecting different biomarkers to simultaneously monitor and manage infection in combat as well as chronic wounds.

Spotlight on Photoactivatable Liposomes beyond Drug Delivery: An Enabler of Multitargeting of Molecular Pathways.

The potential of photoactivating certain molecules, photosensitizers (PS), resulting in photochemical processes, has long been realized in the form of photodynamic therapy (PDT) for the management of several cancerous and noncancerous pathologies. With an improved understanding of the photoactivation process and its broader implications, efforts are being made to exploit the various facets of photoactivation, PDT, and the associated phenomenon of photodynamic priming in enhancing treatment outcomes, specifically in cancer therapeutics. The parallel emergence of nanomedicine, specifically liposome-based nanoformulations, and the convergence of the two fields of liposome-based drug delivery and PDT have led to the development of unique hybrid systems, which combine the exciting features of liposomes with adequate complementation through the photoactivation process. While initially liposomes carrying photosensitizers (PSs) were developed for enhancing the pharmacokinetics and the general applicability of PSs, more recently, PS-loaded liposomes, apart from their utility in PDT, have found several applications including enhanced targeting of drugs, coloading multiple therapeutic agents to enhance synergistic effects, imaging, priming, triggering drug release, and facilitating the escape of therapeutic agents from the endolysosomal complex. This review discusses the design strategies, potential, and unique attributes of these hybrid systems, with not only photoactivation as an attribute but also the ability to encapsulate multiple agents for imaging, biomodulation, priming, and therapy referred to as photoactivatable multiagent/inhibitor liposomes (PMILS) and their targeted versions─targeted PMILS (TPMILS). While liposomes have formed their own niche in nanotechnology and nanomedicine with several clinically approved formulations, we try to highlight how using PS-loaded liposomes could address some of the limitations and concerns usually associated with liposomes to overcome them and enhance their preclinical and clinical utility in the future.

Multifunctional chitosan ferrogels for targeted cancer therapy by on-demand magnetically triggered drug delivery and hyperthermia

A facile method for the synthesis of chitosan ferrogels for magnetically triggered drug release and hyperthermia treatment is presented. The glyoxal crosslinked, dried ferrogels (magnetic bioaerogels) have been characterized by FTIR, XRD, TGA and VSM analyses and they possess unique characteristics such as high porosity, ultra-low density and superparamagnetism (Ms up to 56 emu g−1). In addition, they present high drug (Doxorubicin, DOX) loading efficiency (~40 %), tumor-specific pH-responsive swelling, excellent biodegradation, remotely switchable drug release and high magnetic hyperthermia potential (42 °C within 4 min). Almost complete degradation of the ferrogels occurs in 3 months under physiological conditions (pH = 7.4), while the tumor-specific microenvironment (pH = 5.6) accelerates the degradation rate, where it occurs in ~8 weeks. Furthermore, an enhancement in drug release (by 30 %) was observed in 60 min, when subjected to a magnetic field of 50 mT. Excellent biocompatibility and promising cell-material interactions have been exhibited by the ferrogels, substantiated by MTT assay, cytoskeleton staining and confocal imaging. The viability has been drastically reduced for DOX-loaded samples due to the action of the released drug; validating the efficacy of DOX loaded ferrogels. The system presented, therefore, holds multi-functionalities enabling smart cancer treatment.