Liposomal Carrier Research Articles

Enhancement of in vitro antitumour activity of epirubicin in HER2+ breast cancer cells using immunoliposome formulation.

Epirubicin (EPI) is one of the potent breast cancer (BC) chemotherapeutic agents, but its adverse effects limit its efficacy. Herein, EPI was selected to be loaded in liposomal carrier, which has been targeted by a monoclonal antibody, Herceptin. The preparation process of liposomes was a modified ethanol injection method followed by Herceptin conjugation. The in vitro cell toxicity and cellular uptake of optimum formulation against HER2+ and HER2− cancer cell lines were evaluated. The results showed that the drug loading (DL%) and encapsulation efficiency (EE%) of liposome preparation method yielded 30.62% ± 0.49% and 62.39% ± 8.75%, respectively. The average size of naked liposomes (EPI‐Lipo) and immunoliposomes (EPI‐Lipo‐mAb) was 234 ± 9.86 and 257.26 ± 6.25 nm, with a relatively monodisperse distribution, which was confirmed by SEM micrographs. The release kinetic followed Higuchi model for both naked and immunoliposomes. In vitro cytotoxicity study on three different BC cell lines including BT‐20, MDA‐MB‐453 and MCF‐7 demonstrated higher toxicity of EPI in the Herceptin conjugated form (EPI‐Lipo‐mAb) in comparison with the free EPI and EPI‐Lipo in HER2 overexpressing cell line. In addition, the cellular uptake study showed a higher uptake of immunoliposomes by MCF‐7 cells in comparison with naked liposomes. In conclusion, these data show that the targeted delivery of EPI to breast cancer cells can be achieved by EPI‐Lipo‐mAb in vitro, and this strategy could be used for breast cancer therapy with further studies.

Effect of pH on Isoliquiritigenin (ISL) fluorescence in lipo- polymeric system and metallic nanosystem

Flavonoids have various medicinal properties such as anti-inflammatory, anti-oxidant, anti-cancer, antiviral. Yet, the fluorescent properties of flavonoids are less explored and termed as autofluorescence in general. This study investigates the fluorescence properties of Isoliquiritigenin (ISL) in various alkaline conditions. The maximum fluorescence emission was obtained at pH 12 on excitation wavelength of 440 nm. Theoretical and experimental investigation on the shift in UV–Vis absorbance spectra, upon the variation in pH, performed, indicated deprotonation as the cause. PEG-based stable liposome carrier, with an internal alkaline environment (LIP-ISL-NaOH) that aids in flavonoid fluorescence, was synthesized using a modified thin-film hydration method. The hydrodynamic size of the liposome synthesized was in the range of 50–70 nm. PEG, on the addition, found maintaining the alkaline environment in the internal chamber of the lipo-polymer system, helps the LIP-ISLNaOH nanosystem to exhibit fluorescence irrespective of the suspension pH. Further, reducing property of ISL was used for the synthesis of Au nanoclusters to achieve theranostic nature.

Electrophysiological characterization of the activating action of a novel liposomal nitric oxide carrier on Maxi-K channels in pulmonary artery smooth muscle cells

The aim of this study was to establish the mechanisms of action of a novel liposomal nitric oxide (NO) carrier on large-conductance Ca2+-activated channels (BKCa or Maxi-K) expressed in vascular smooth muscle cells (VSMCs) isolated from the rat main pulmonary artery (MPA). Experimental design comprised of both whole-cell and cell-attached single-channel recordings using the patch-clamp techniques. The liposomal form of NO, Lip(NO), increased whole-cell outward K+ currents in a dose dependent manner while shifting the activation curve negatively by about 50 mV with respect to unstimulated cells with the EC50 value of 0.55 ± 0.17 µM. At the single channel level, Lip(NO) increased the probability of the open state (Po) of Maxi-K channels from 0.0020 ± 0.0008 to 0.74 ± 0.02 with half-maximal activation occurring at 4.91 ± 0.01 μM, while sub-maximal activation was achieved at 10−5 M Lip(NO). Channel activation was mainly due to significant decrease in the mean closed dwell time (about 500-fold), rather than an increase in the mean open dwell time, which was comparatively modest (about twofold). There was also a slight decrease in the amplitude of the elementary Maxi-K currents (approximately 15%) accompanied by an increase in current noise, which might indicate some non-specific effects of Lip(NO) on the plasma membrane itself and/or on the phospholipids environment of the channels. In conclusion, the activating action of Lip(NO) on the Maxi-K channel is due to the destabilization of the closed conformation of the channel protein, which causes its more frequent openings and, accordingly, increases the probability of channel transition to its open state.

Building Blocks to Design Liposomal Delivery Systems.

The flexibility of liposomal carriers does not just simply rely on their capability to encapsulate various types of therapeutic substances, but also on the large array of components used for designing liposome-based nanoformulations. Each of their components plays a very specific role in the formulation and can be easily replaced whenever a different therapeutic effect is desired. It is tempting to describe this by an analogy to Lego blocks, since a whole set of structures, differing in their features, can be designed using a certain pool of blocks. In this review, we focus on different design strategies, where a broad variety of liposomal components facilitates the attainment of straightforward control over targeting and drug release, which leads to the design of the most promising systems for drug delivery. The key aspects of this block-based architecture became evident after its implementation in our recent works on liposomal carriers of antisense oligonucleotides and statins, which are described in the last chapter of this review.

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release.

Simple SummaryA novel active release system magnetic sphingomyelin-containing liposome encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin was evaluated. The liposomal sphingomyelin is a target for the sphingomyelinase enzyme, which is released by stressed cells. Thus, sphingomyelin containing liposomes behave as a sensitizer for biological stress situations. In addition, the liposomes were engineered by adding paramagnetic beads to act as a receiver of outside given magnetic energy. The enzymatic activity towards liposomes and destruction caused by the applied magnetic field caused the release of the content from the liposomes. By using these novel liposomes, we could improve the drug release feature of liposomes. The improved targeting and drug-release were shown in vitro and the orthotopic tongue cancer model in mice optical imaging. The increased delivery of cisplatin prolonged the survival of the targeted delivery group versus free cisplatin.Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.

Lectin Protein as a Promising Component to Functionalize Micelles, Liposomes and Lipid NPs against Coronavirus.

The outbreak of a novel strain coronavirus as the causative agent of COVID-19 pneumonia, first identified in Wuhan, China in December 2019, has resulted in considerable focus on virulence abilities of coronavirus. Lectins are natural proteins with the ability to bind specific carbohydrates related to various microorganisms, including viruses, bacteria, fungi and parasites. Lectins have the ability to agglutinate and neutralize these pathogeneses. The delivery of the encapsulated antiviral agents or vaccines across the cell membrane can be possible by functionalized micellar and liposomal formulations. In this mini-review, recent advances and challenges related to important lectins with inhibition activities against coronaviruses are presented to obtain a novel viewpoint of microformulations or nanoformulations by micellar and liposomal cell-binding carriers.

Development of a pathogenesis-based therapy for peeling skin syndrome type 1.

Peeling skin syndrome type 1 (PSS1) is a rare and severe autosomal recessive form of congenital ichthyosis. Patients are affected by pronounced erythroderma accompanied by pruritus and superficial generalized peeling of the skin. The disease is caused by nonsense mutations or complete deletion of the CDSN gene encoding for corneodesmosin (CDSN). PSS1 severely impairs quality of life and therapeutic approaches are totally unsatisfactory. The objective of this study was to develop the first steps towards a specific protein replacement therapy for CDSN deficiency. Using this approach, we aimed to restore the lack of CDSN and improve cell-cell cohesion in the transition area of the stratum granulosum (SG) to the stratum corneum. Human CDSN was recombinantly expressed in Escherichia coli. A liposome-based carrier system, prepared with a cationic lipopeptide to mediate the transport to the outer membrane of keratinocytes, was developed. This formulation was chosen for CDSN delivery into the skin. The liposomal carrier system was characterized with respect to size, stability and toxicity. Furthermore, the interaction with primary keratinocytes and human epidermal equivalents was investigated. The liposomes showed an accumulation at the membranes of keratinocytes. CDSN-deficient epidermal equivalents that were treated with liposomal encapsulated CDSN demonstrated presence of CDSN in the SG. Finally, the penetration assay and histological examinations revealed an improved epidermal integrity for CDSN-deficient epidermal equivalents, if they were treated with liposomal encapsulated CDSN. This study presents the first preclinical in vitro experiments for a future specific protein replacement therapy for patients affected by PSS1.

Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+ CD169+ monocytes and Axl+ CD169+ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+ moDCs and Axl+ CD169+ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+ T cells. Finally, Axl+ CD169+ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+ DCs to drive antitumor T cell responses.

Traditional Herbal Medicines, Newer Herbs and Other Novel Approaches Integrated in Herbal Medicine for Atopic Dermatitis-A Narrative Review

Atopic Dermatitis (AD) is a prolonged reverting skin ailment with characteristically distributed skin lesions. In the previous decades, researchers had shown a marked interest in AD due to its increased prevalence in developed countries. Although different strategies including biological and immune modulators are available for the treatment of AD, each has certain limitations. The researchers had shown considerable interest in the management of AD with herbal medicines. The establishment of herbal drugs for AD might eliminate local as well as systemic adverse effects associated with long term use of corticosteroids and also higher cost of therapy with biological drugs. The present review discusses the traditional East Asian herbal medicines and scientific data related to newer herbal extracts or compositions for the treatment of AD. In vivo animal models and in vitro cell cultures, investigated with herbal medicines to establish a possible role in AD treatment, have also been discussed in the paper. The paper also highlights the role of certain new approaches, i.e. pharmacopuncture, a combination of allopathic and herbal medicines; and novel carriers (liposomes, cubosomes) for herbal drugs on atopic skin. In conclusion, herbal medicines can be a better and safe, complementary and alternative treatment option for AD.

Liposomal Carrier Conjugated to APP-Derived Peptide for Brain Cancer Treatment.

Braintumors are hard to treat with the currently available therapy. The major obstacle in the treatment of brain tumors is the lack of therapeutic strategies capable to penetrate the blood-brain barrier (BBB). The BBB is an endothelial interface that separates the brain from the circulatory blood system and prevents the exposure of the central nervous system (CNS) to circulating toxins and potentially harmful compounds. Unfortunately, the BBB prevents also the penetration of therapeutic compounds into the brain. We present here a drug-delivery liposomal carrier, conjugated to a peptide inserted in the liposomal membrane, which is putatively recognized by BBB transporters. The peptide is a short sequence of 5 amino acids (RERMS) present in the amyloid precursor protein (APP). This APP-targeted liposomal system was designed specifically for transporting compounds with anti-cancer activity via the BBB into the brain in an effective manner. This drug-delivery liposomal carrier loaded with the anti-cancer compounds temozolomide (TMZ), curcumin, and doxorubicin crossed the BBB in an in vitro model as well as in vivo (mice model). In the in vitro model, the targeted liposomes crossed the BBB model fourfold higher than the non-targeted liposomes. Labeled targeted liposomes penetrated the brain in vivo 35% more than non-targeted liposomes. Treatment of mice that underwent intracranial injection of human U87 glioblastoma, with the targeted liposomes loaded with the three tested anti-cancer agents, delayed the tumor growth and prolonged the mice survival in a range of 45% -70%. It appears that the targeted liposomal drug-delivery system enables better therapeutic efficacy in a SCID mouse model of glioblastoma compared to the corresponding non-targeted liposomes and the free compounds.

Liposomal Dual Delivery of Both Polysaccharide and Protein Antigens.

Pneumococcal disease is caused by Streptococcus pneumoniae, a colonizing microorganism characterized by transitioning from a benign commensal to a virulent pathogen in the presence of suitable circumstances, which then poses a serious infectious disease threat afflicting millions of people. Especially affected are the young and elderly through outcomes that include pneumonia, bacteremia, meningitis, and otitis media. Current prevention vaccine options on the market contain capsular polysaccharides conjugated to the Diphtheria CRM197 protein (Pfizer) or are composed of only pneumococcal polysaccharides (Merck), and in both cases, limitations prevent the generation of comprehensive disease protection. Through the use of a liposomal carrier, we present an alternative methodology for producing a vaccine product via noncovalent colocalization of both polysaccharide and protein classes of complementary pneumococcal disease immunogens.

Liposomal Delivery of Mitoxantrone and a Cholesteryl Indoximod Prodrug Provides Effective Chemo-immunotherapy in Multiple Solid Tumors.

We developed a custom-designed liposome carrier for codelivery of a potent immunogenic cell death (ICD) stimulus plus an inhibitor of the indoleamine 2,3-dioxygenase (IDO-1) pathway to establish a chemo-immunotherapy approach for solid tumors in syngeneic mice. The carrier was constructed by remote import of the anthraquinone chemotherapeutic agent, mitoxantrone (MTO), into the liposomes, which were further endowed with a cholesterol-conjugated indoximod (IND) prodrug in the lipid bilayer. For proof-of-principle testing, we used IV injection of the MTO/IND liposome in a CT26 colon cancer model to demonstrate the generation of a robust immune response, characterized by the appearance of ICD markers (CRT and HMGB-1) as well as evidence of cytotoxic cancer cell death, mediated by perforin and granzyme B. Noteworthy, the cytotoxic effects involved natural killer (NK) cell, which suggests a different type of ICD response. The immunotherapy response was significantly augmented by codelivery of the IND prodrug, which induced additional CRT expression, reduced number of Foxp3+ Treg, and increased perforin release, in addition to extending animal survival beyond the effect of an MTO-only liposome. The outcome reflects the improved pharmacokinetics of MTO delivery to the cancer site by the carrier. In light of the success in the CT26 model, we also assessed the platform efficacy in further breast cancer (EMT6 and 4T1) and renal cancer (RENCA) models, which overexpress IDO-1. Encapsulated MTO delivery was highly effective for inducing chemo-immunotherapy responses, with NK participation, in all tumor models. Moreover, the growth inhibitory effect of MTO was enhanced by IND codelivery in EMT6 and 4T1 tumors. All considered, our data support the use of encapsulated MTO delivery for chemo-immunotherapy, with the possibility to boost the immune response by codelivery of an IDO-1 pathway inhibitor.

Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells

ABSTRACT Background Multidrug resistance (MDR) limits the beneficial outcomes of conventional breast cancer chemotherapy. Ras-related nuclear protein (Ran-GTP) plays a key role in these resistance mechanisms, assisting cancer cells to repair damage to DNA. Herein, we investigate the co-delivery of Ran-RCC1 inhibitory peptide (RAN-IP) and doxorubicin (DOX) to breast cancer cells using liposomal nanocarriers. Research design A liposomal delivery system, co-encapsulating DOX, and RAN-IP, was prepared using a thin-film rehydration technique. Dual-loaded liposomes were optimized by systematic modification of formulation variables. Real-Time-Polymerase Chain Reaction was used to determine Ran-GTP mRNA expression. In vitro cell lines were used to evaluate the effect of loaded liposomes on the viability of breast and lung cancer cell lines. In vivo testing was performed on a murine Solid Ehrlich Carcinoma model. Results RAN-IP reversed the Ran-expression-mediated MDR by inhibiting the Ran DNA damage repair function. Co-administration of RAN-IP enhanced sensitivity of DOX in breast cancer cell lines. Finally, liposome-mediated co-delivery with RAN-IP improved the anti-tumor effect of DOX in tumor-bearing mice when compared to single therapy. Conclusions This study is the first to show the simultaneous delivery of RAN-IP and DOX using liposomes can be synergistic with DOX and lead to tumor regression in vitro and in vivo.

Liposomal/Nanoliposomal Encapsulation of Food-Relevant Enzymes and Their Application in the Food Industry

A liposomal vesicular structure is composed of one or more phospholipid bilayers in an aqueous environment. Liposomes are the most popular carriers used to design a delivery system for different compounds in the pharmacological, biochemical, biological, food, and agricultural sectors. Enzymes are commonly used ingredients in food industries, such as bakery, dairy, and beverages. Nevertheless, they are very sensitive to environmental stresses and harsh processing conditions and it is not possible to have a controlled release profile for their free forms. Fortunately, these limitations can be overcome by loading the enzymes in an efficient encapsulation system such as liposomal carriers. Many studies have indicated that the liposomes can be a proper candidate for encapsulation and delivery of enzymes. In this study, preparation and application of food-grade liposomes for encapsulation of a variety of enzymes have been reviewed and discussed. Particularly, application of enzyme-loaded liposomes for acceleration of ripening in different cheeses and various catalyzed reactions by liposomal enzymes have been covered.

LipoBots: Using Liposomal Vesicles as Protective Shell of Urease‐Based Nanomotors

AbstractDeveloping self‐powered nanomotors made of biocompatible and functional components is of paramount importance in future biomedical applications. Herein, the functional features of LipoBots (LBs) composed of a liposomal carrier containing urease enzymes for propulsion, including their protective properties against acidic conditions and their on‐demand triggered activation, are reported. Given the functional nature of liposomes, enzymes can be either encapsulated or coated on the surface of the vesicles. The influence of the location of urease on motion dynamics is first studied, finding that the surface‐urease LBs undergo self‐propulsion whereas the encapsulated‐urease LBs do not. However, adding a percolating agent present in the bile salts to the encapsulated‐urease LBs triggers active motion. Moreover, it is found that when both types of nanomotors are exposed to a medium of similar pH found in the stomach, the surface‐urease LBs lose activity and motion capabilities, while the encapsulated‐urease LBs retain activity and mobility. The results for the protection enzyme activity through encapsulation within liposomes and in situ triggering of the motion of LBs upon exposure to bile salts may open new avenues for the use of liposome‐based nanomotors in drug delivery, for example, in the gastrointestinal tract, where bile salts are naturally present in the intestine.

Particle Design Strategies for Developing Patient Centric Dosage Form Preparations

Novel dosage form designs aiming at patient centric drug therapy are summarized here based on my carrier research in this field. The common key word for this research is particle design. The topics will be divided into two parts, based on the type of particle: coarse particles (powder) and colloidal particles. The former includes the preparation and characterization of functional particles prepared using a spray dryer. Solid dispersions, solvent deposition particles and dry emulsion systems are described. Polymer coated liposomes are described as a useful drug delivery carrier in several administration routes. As chitosan, a mucoadhesive polymer, was used as a coating polymer, the resultant chitosan-coated liposome was found to work as a good carrier for peptide drugs such as insulin and calcitonin in the gastrointestinal tract after oral administration. In another administration route (inhalation), polymer-coated liposomes enhanced the absorption of the drugs. Liposomal carriers applied to the surface of the eye as eye drops are able to deliver drugs to the posterior part of the eye, such as the retina. As a typical example of patient centric dosage form design, particle designs for the preparation of orally disintegrating tablets and films were introduced in one of our recent studies on oral dosage form design.

Functionally engineered 'hepato-liposomes': Combating liver-stage malaria in a single prophylactic dose.

Primaquine continues to remain the gold standard molecule with an incumbent toxicity profile, as far as radical treatment of malaria is concerned. Better molecules are available at experimental level but their targeted delivery is a challenge. The present work identifies 'Decoquinate (DQN)' as a repurposed, safer drug molecule with a potential to function as an appealing replacement for primaquine active against liver-stage malaria. The work focuses on delivering the highly lipophilic DQN (log P~5) in a liposomal carrier system to 'sporozoite infested hepatocytes' using two different in-house synthesized hepatotropic ligands. Functionally engineered 'hepato-liposomes' exhibit differences in their DQN loading capacities but no significant change in morphology or particle size and are also not affected by freeze drying. Two ligands, targeting different receptors on hepatocytes, have been compared for their in vitro and in vivo drug delivery efficiency in liver stage malaria. The studies reveal superior antimalarial efficacy of differently designed DQN loaded liposomes and demonstrate antimalarial efficacy at a low dose of 0.5mg/kg for a repurposed molecule like DQN. The in vivo studies successfully discriminate the functional efficiency of the carriers and establish the importance of design in liposomal drug delivery for malarial prophylaxis.

Improving the physicochemical stability and functionality of nanoliposome using green polymer for the delivery of pelargonidin-3-O-glucoside

This study aimed to improve the physicochemical stability of nanoliposome (NL) with enhanced functionality for the delivery of Pelargonidin-3-O-glucoside (P3G) using biopolymers, i.e. chitosan (CH) and pectin (P). In this study, we successfully developed stabilized liposomal carriers, i.e. CH-conjugated NL (CH-NL) and P-conjugated CH-NL (P-CH-NL) using an optimum concentration of CH (0.6 wt%) and P (0.5 wt%). Results revealed that P-CH-NL had better physical stability to salt and pH with maximum P3G retention (>97%) under oxidative, thermal, and UV conditions. Nanoliposomes were more stable under refrigerated-storage and ensured high P3G retention (>96%). In vitro mucoadhesion study revealed that CH-NL had better mucin adsorption efficiency (59.72%) followed by P-CH-NL and NL. Furthermore, CH-NL and P-CH-NL alternatively had better stability to serum than NL. Taken together, the stabilization of nanoliposome using chitosan and pectin can be a promising approach for the delivery of hydrophilic compounds in association with enhanced stability and functionality.

Photosensitizer-Doped and Plasma Membrane-Responsive Liposomes for Nuclear Drug Delivery and Multidrug Resistance Reversal.

Clinically approved doxorubicin (Dox)-loaded liposomes (e.g., Doxil) guarantee good biosafety, but their insufficient nuclear delivery of Dox (<0.4%) after cellular uptake significantly hampers their final anticancer efficacy. Here, we report that simply doping protoporphyrin IX (PpIX, a commonly used hydrophobic photosensitizer) into the lipid bilayers of Dox-loaded liposomes (the resultant product is termed PpIX/Dox liposomes) is a feasible way to promote the nuclear delivery of Dox. This facile strategy relies on a unique property of PpIX-it presents considerably higher affinity for the real plasma membrane over its liposomal carrier, which drives the doped PpIX molecules to detach from the liposomes when encountering cancer cells. We demonstrate that this process can trigger the efficient release of the loaded Dox molecules and allow them to enter the nuclei of MCF-7 breast cancer cells without being trapped by lysosomes. Regarding the drug-resistant MCF-7/ADR cells, the aberrant activation of the efflux pumps in the plasma membranes expels the internalized Dox. However, we strikingly find that the robust drug resistance can be reversed upon mild laser irradiation because the photodynamic effect of PpIX disrupts the drug efflux system (e.g., P-glycoprotein) and facilitates the nuclear entry of Dox. As a proof-of-concept, this PpIX doping strategy is also applicable for enhancing the effectiveness of cisplatin-loaded liposomes against both A549 and A549/DDP lung cancer cells. In vivo experimental results prove that a single injection of PpIX/Dox liposomes completely impedes the growth of MCF-7 tumors in nude mice within 2 weeks and, in combination with laser irradiation, can synergistically ablate MCF-7/ADR tumors. Biosafety assessments reveal no significant systemic toxicity caused by PpIX/Dox liposomes. This work exemplifies a facile method to modulate the subcellular fate of liposomal drugs and may inspire the optimization of nanopharmaceuticals in the near future.

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes.

A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier.