Albumin Nanoparticles Research Articles

In vitro and in vivo study on the anticancer effects of anethole-loaded bovine serum albumin nanoparticles surface decorated with chitosan and folic acid

Anethole (Ant) is a herbal compound with unique properties, which is limited in its clinical use due to its low solubility in aqueous solutions. Therefore, in this study, albumin nanocarrier modified with chitosan-folate was used to transfer Ant to cancer cells and its anticancer effects were evaluated. First, Ant was loaded on albumin nanoparticles by desolvation method and then the surface of nanoparticles was covered with chitosan bound to folate. After characterization, the amount of Ant loading in nanoparticles was measured by the absorption method and then its toxicity effects on breast cancer cell lines, colon, and normal cells were evaluated by the MTT method. The real-time QPCR method was used to investigate the expression changes of apoptosis-related genes in the treated cells compared to the control cells, and finally, the antitumor effects of nanoparticles were evaluated in the mouse model carrying breast cancer. The results of this investigation showed the presence of nanoparticles with dimensions of 252 nm, a dispersion index of 0.28 mV, and a surface charge of 27.14 mV, which are trapped in about 88% of ATL. The toxicity effect of nanoparticles was shown on breast, colon, and normal cancer cells, respectively. In addition, the examination of the gene profile under investigation showed an increase in the expression of BAX and caspase-3 and -9 along with a decrease in the expression of the Bcl-2 gene, which confirms the activation of the internal pathway of apoptosis. The decrease in the volume of tumors and the presence of apoptotic areas in the tissue sections confirmed the antitumor effects of nanoparticles in the in vivo model. The inhibition percentage of free Ant and nanoparticles with a concentration of 25 and 50 mg/kg/tumor volume was reported as 36.9%, 56.6%, and 64.9%, respectively, during 15 days of treatment. These results showed the effectiveness of the formulation in inhibiting cancer cells both in vitro and in vivo.

Novel nanotherapeutics for cancer immunotherapy by CTLA-4 aptamer-functionalized albumin nanoparticle loaded with antihistamine.

Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has generated remarkable clinical results against multiple malignancies. Exploration of new technical approaches to further boost the therapeutic efficacy of ICB is of potential medical importance. In this study, we designed a novel nanotherapeutics for ICB immunotherapy. CTLA-4 aptamers were conjugated to the surface of albumin nanoparticle to construct an aptamer-modified nanostructure (Apt-NP). To improve ICB efficacy, fexofenadine (FEXO), an antihistamine, was encapsulated into Apt-NP to make a drug-loaded nanoparticle (Apt-NP-FEXO).Theantitumor efficacies of Apt-NP and Apt-NP-FEXO were evaluated in vitro and in vivo. Apt-NP and Apt-NP-FEXO had average diameters of 149nm and 159nm, respectively. Similar to free CTLA-4 aptamers, Apt-modified NPs could selectively bind with CTLA-4 positive cells and improve lymphocyte-mediated antitumor cytotoxicity in vitro. In animal studies, compared with free CTLA-4 aptamer, Apt-NP significantly enhanced antitumor immunity. Moreover, Apt-NP-FEXO further improved antitumor efficacy vs. Apt-NP in vivo. The results suggest that Apt-NP-FEXO represents a novel strategy to improve ICB outcome and may have application potential in cancer immunotherapy.

Neutrophil Camouflaged Stealth Nanovehicle for Photothermal-Induced Tumor Immunotherapy by Triggering Pyroptosis.

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b- and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.

Bio-Entities Based on Albumin Nanoparticles and Biomimetic Cell Membranes: Design, Characterization and Biophysical Evaluation

Protein-based particles are one of the most important research topics in nanomedicine, being used especially as drug delivery systems. From the wide variety of proteins, albumins offer several advantages in biomedical applications due to their special properties. Albumin nanoparticles play an important role as carriers in the drug delivery of chemical and biomolecular drugs, such as anticancer drugs; offer many advantages, such as biocompatibility and biodegradability; and are well-tolerated, without any side effects. In this work, various types of bovine serum albumin nanoparticles (BSA NPs), with or without ascorbic acid or glucose, were prepared via different nanoprecipitation methods. The obtained BSA NPs were characterized by UV–Vis absorption spectroscopy. Their size and morphology were studied by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The stability in time of the developed BSA NPs was spectrally monitored. Three types of bio-entities containing BSA NPs and chlorophyll-labeled artificial cell membranes were “green” developed. The designed biohybrids were characterized by UV–Vis absorption and fluorescence emission spectroscopy, and their three-dimensional topography was investigated by AFM. Both the size and shape of the developed bio-entities were monitored through SEM analysis. These results could be exploited in the development of novel drug carrier systems or as bio-coatings to be used in the biomedical field.

Co-delivery of paclitaxel and etoposide prodrug by human serum albumin and PLGA nanoparticles: synergistic cytotoxicity in brain tumour cells

The aims of this study were to develop co-delivery systems of paclitaxel (PTX) and etoposide prodrug (4’-O-benzyloxycarbonyl-etoposide, ETP-cbz) based on non-cross-linked human serum albumin (HSA) and poly(lactide-co-glycolide) nanoparticles and to evaluate the synergistic potential of these drugs in vitro. The nanoformulations were prepared by the high-pressure homogenisation technique and characterised using DLS, TEM, SEM, AFM, HPLC, CZE, in-vitro release, and cytotoxicity in human and murine glioma cells. All nanoparticles had 90-150 nm in size and negative ζ-potentials. The Neuro2A cells were the most sensitive to both HSA- and PLGA-based co-delivery systems (IC50 0.024 µM and 0.053 µM, respectively). The drugs’ synergistic effect (combination index < 0.9) was observed in the GL261 cells for both types of co-delivery formulations and in the Neuro2A cells for the HSA-based system. These nanodelivery systems may be useful to improve combination chemotherapy for brain tumour treatment. To our knowledge, this is the first report describing the non-cross-linked HSA-based co-delivery nanosuspension which was prepared using nab™ technology.

Therapeutic efficacy of albendazole and berberine loaded on bovine serum albumin nanoparticles on intestinal and muscular phases of experimental trichinellosis

There has been no treatment for trichinellosis until now. Therefore, this work targeted to investigating the efficacy of albendazole and berberine alone and loaded on bovine serum albumin (BSA) nanoparticles against intestinal and muscular phases of trichinellosis in mice. Mice were divided into nine different groups: negative control, positive control, blank nanoparticle, albendazole, berberine, a combination of albendazole and berberine, albendazole-loaded nanoparticle, berberine-loaded nanoparticle and combination of albendazole and berberine-loaded nanoparticle. Subsequently, they were sacrificed 6 and 35 days after infection. Treatment efficacies were parasitologically, histopathologically and, immunohistochemically assessed. Parasitological counting for the adult worms and encysted larvae with histopathological assessment using H&E for intestinal and muscular sections and picrosirius red stain for muscular sections were used. Also, immunohistochemical expression of the intestinal nod-like receptor-pyrin domain containing 3 (NLRP3) was investigated. The group treated with nano_combined drugs showed a statistically significant reduction in adult and encysted larval count (p<0.005), a remarkable improvement of intestinal and muscular inflammation, and a reduction in the capsular thickness of the larvae. Also, this group showed the highest reduction of NLRP3 expression. This work revealed that berberine might be a promising anti-trichinellosis drug with a synergistic effect when combined with albendazole through modulation of the immune response, inflammation, and larva capsule formation. Furthermore, delivering both drugs in a nanoparticle form improves their therapeutic response.

Novel Nanotherapeutics for Cancer Immunotherapy by PD-L1-Aptamer-Functionalized and Fexofenadine-Loaded Albumin Nanoparticles.

Immune checkpoint blockade (ICB) is an important strategy for cancer treatment and has achieved remarkable clinical results. Further enhancement of the efficacy of ICB therapy with a new technical approach is of potential medical importance. In this study, we constructed a novel nanotherapeutic agent (PDL1-NP-FEXO) for cancer immunotherapy by attaching PD-L1 aptamers to albumin nanoparticles that were loaded with H1-antihitamine fexofenadine (FEXO). FEXO has been reported to enhance the immunotherapy response by reducing the immunosuppressive M2-like macrophages in the tumor microenvironment. The albumin nanoparticle was fabricated using a self-assembly method. A dynamic light scattering (DLS) study revealed that the average size of PD-L1 aptamer-modified nanoparticle without FEXO (PDL1-NP) was 135.5 nm, while that of PDL1-NP-FEXO was 154.6 nm. Similar to free PD-L1 aptamer, PDL1-NP could also bind with PD-L1-expressing tumor cells (MDA-MB-231). Of note, compared with free PD-L1 aptamer, PDL1-NP significantly boosted tumor inhibition in CT26-bearing mice. Moreover, PDL1-NP-FEXO further enhanced the antitumor efficacy vs. PDL1-NP in an animal model, without raising systemic toxicity. These results indicate that PDL1-NP-FEXO represents a promising strategy to improve ICB efficacy and may have application potential in cancer immunotherapy.

Synthesis and Characterization of Alpinia calcarata Loaded Nanoparticles to Control Hyperglycemia

Bovine Serum Albumin (BSA) nanoparticles loaded with the bioactive compounds of A. calcarata, which is known to exert its antidiabetic activity through the inhibition of pancreatic enzymes, are a good form of an antidiabetic nutraceutical as they have reduced side effects, protection of active compounds from environmental agents, specific delivery to target sites and prolonged shelf-life. The objective of the present study was to synthesize and characterize A. calcarata loaded nanoparticles (ALNP) to be used as a powder form nutraceutical with higher antidiabetic activity. In this study an aqueous A. calcarata extract (4.00 mL) was added to BSA (20 mg/mL, 4.00 mL, pH 9) in the presence of citric acid as the cross-linking agent. The ALNP gave an IC50 value of 147 µg/mL, a glucose (5 mM) uptake percentage of 73.09% at a 0.5 mg/mL concentration, a solubility value of 64%, A. calcarata loading percentage of 6.66% and A. calcarata entrapment efficiency of 87.71%. They had a spherical morphology and uniform size with a particle size of 1030.70 nm, PDI of 0.199 and a zeta potential of 2.57 mV. The UV-Visible absorbance spectra and FT-IR spectra showed that citric acid had caused conformational changes in the protein structure of BSA and that the active compounds were successfully loaded into the synthesized nanoparticles which interacted with the protein matrix via covalent bonds. Therefore, it can be concluded that the synthesized nanoparticles have an antidiabetic effect and the antidiabetic activity of bioactive compounds of the aqueous A. calcarata extract become enhanced when loaded onto the nanocarriers.

Highly specific neutrophil-mediated delivery of albumin nanoparticles to ectopic lesion for endometriosis therapy

Endometriosis is an estrogen-dependent chronic inflammatory disease. Hormonal and surgical treatments are the most commonly used clinical therapies, but they have many sides effects or are traumatic to the body. Therefore, specific drugs for endometriosis treatment are urgently needed to develop. In this study, we identified two features of endometriosis, namely the continuous recruitment of neutrophils into the ectopic lesions and the higher uptake of glucose by ectopic cells. For the above features, we designed a glucose oxidase-loaded bovine serum albumin nanoparticle (BSA-GOx-NPs) that is inexpensive and facilitates large-scale production. After injection, BSA-GOx-NPs were high specifically delivered to ectopic lesions in a neutrophil-dependent manner. Furthermore, BSA-GOx-NPs deplete glucose and induce apoptosis in the ectopic lesions. Whereupon BSA-GOx-NPs produced excellent anti-endometriosis effects when administrated in both acute and chronic inflammatory phases. These results reveal for the first time that the neutrophil hitchhiking strategy is effective in chronic inflammatory disease and provide a non-hormonal and easy-to-achieve approach for endometriosis treatment.

Sisplatin ve Karboplatin Yüklü Albumin Nanopartiküllerin Meme Kanseri Hücreleri Üzerindeki Sitotoksik Etkileri

Objective: This study aims to investigate and compare the anticancer effects of carboplatin and cisplatin, frequently used in cancer treatment, by loading them on albumin nanocarrier. Materials and Methods: Carboplatin (CP) and Cisplatin (Cis) loaded albumin nanoparticles were synthesized using ultrasonication as CP-NPs and Cis-NPs, respectively. Nanoparticle size and distribution were evaluated by Dynamic light scattering (DLS). Cytotoxicities of NPs were evaluated in MDA-MB-231 and MCF-7 breast cancer cells and HUVEC using MTT test and their morphological images were compared. Results: While the average size of CP-NPs was around 2-3 nm, Cis-NPs was 7-8 nm. It was observed that both NPs groups were homogeneously dispersed. According to the cytotoxicity results, both CP-NPs and Cis-NPs were more cytotoxic on MCF-7 breast cancer cells. In addition, CP-NPs and Cis-NPs showed significant cytotoxicity on MCF-7, MDA-MB-231 breast cancer cells, while low cytotoxicity was detected in normal HUVEC cells. The NPs treated MCF-7 was compared with the untreated MCF-7 and statistical significance was calculated as P&amp;lt;0.01 for CP-NPs and Cis-NPs. Conclusions: Abumin-based CP-NPs and Cis-NPs showed high cytotoxicity in breast cancer cells, they have low cytotoxicity in healthy cells, making them promising for breast cancer treatment.

Cross-frontal mode: An alternative methodology for Taylor dispersion analysis of monomodal sample

Taylor dispersion analysis (TDA) is a technique dedicated to the determination of the molecular diffusion coefficient (D) of species, using band broadening of an analyte in a laminar flow. Two modes are commonly used to perform TDA: pulse and frontal modes. In each case, a fitting of the signal is required. We propose here a third mode denoted as cross-frontal mode, combining two crossed sample fronts without modification of a classical CE device for the rapid and accurate determination of D of caffeine, reduced glutathione (GSH), insulin from bovine pancreas, bovine serum albumin (BSA) and citrate-capped gold nanoparticles (AuNP). Theoretical aspects and methodology are described, showing a good correlation between the so-called cross-frontal mode and usual frontal mode. Limitations of the techniques are also assessed, and are similar to regular modes while no fitting is required. This new methodology allows improving the sensitivity toward low concentrated sample compared to pulse mode, and an alternative mathematical treatment compared to regular TDA modes.

Polysorbate 80-coated albumin nanoparticles to deliver paclitaxel into the brain to treat glioma.

Aim: To develop stable paclitaxel (PTX)-loaded bovine serum albumin (BSA) nanoparticles (BSA-NPs-PTX) as drug-delivery vehicles for delivering paclitaxel into the brain to treat glioma. Methods: This study used PTX-loadedBSA NPs coated with polysorbate 80 (Ps 80) to enhance PTX concentration in the brain. Results: The low IC50 indicated that the fabricated BSA-NPs-PTX and BSA-NPs-PTX-Ps 80 showed significantly enhanced cytotoxicity. The pharmacokinetic and biodistribution analysis of BSA-NPs-PTX and BSA-NPs-PTX 80 showed comparable pharmacokinetic profiles but were significantly different compared with free PTX. Conclusion: BSA-NPs-PTX-Ps 80 exhibited higher plasma concentration-time curves, as compared with BSA-NPs-PTX and PTX. BSA-NPs-PTX and BSA-NPs-PTX-Ps 80 showed significantly improved PTX distribution in the frontal cortex, posterior brain and cerebellum.

PH-responsive nanocomposite hydrogel for simultaneous prevention of postoperative adhesion and tumor recurrence.

Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.

Exploration of the inhibition action of TPGS on tumor cells and its combined use with chemotherapy drugs

D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a commonly used nonionic surfactant used as a pharmaceutical carrier in different drug delivery systems. TPGS can reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) and also has anticancer activities. It suggests that when designing antitumor drug preparation, it’s necessary to take into account the antitumor activity of TPGS. Our in vivo studies showed that TPGS exerted the strongest cytotoxicity in MCF-7-ADR cells when compared with seven other tumor cell lines. The further study revealed TPGS caused apoptosis and blocked MCF-7 cell growth in G2/M phase. Mechanistic insights suggested that TPGS increased intracellular calcium ion concentrations, leading to apoptosis via the mitochondrial pathway. Furthermore, two in vivo experiments were performed. One was TPGS, and DOX solution was administered by tail vein injection on MCF-7-ADR tumor bearing nude mice. The other was temperature sensitive TPGS gel (TPGS-TG) was administered by intratumoral injection on MCF-7-ADR tumor bearing nude mice combined with paclitaxel albumin nanoparticles (Abraxane®) administered by tail vein injection. The findings confirmed that TPGS could play its role in anti-tumor to reduce the toxicity of chemotherapeutic drugs and improve the efficiency of drug-resistant tumors, thereby enhancing the development of safe oncology therapeutics.

Albumin-encapsulated HSP90-PROTAC BP3 nanoparticles not only retain protein degradation ability but also enhance the antitumour activity of BP3 in vivo

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model.

Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline's neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood-brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.

The Anticancer, Anti-metastatic, Anti-oxidant, and Anti-angiogenic Activity of Chitosan-coated Parthenolide/Bovine Serum Albumin Nanoparticles

The Anticancer, Anti-metastatic, Anti-oxidant, and Anti-angiogenic Activity of Chitosan-coated Parthenolide/Bovine Serum Albumin Nanoparticles

Redox-responsive paclitaxel-pentadecanoic acid conjugate encapsulated human serum albumin nanoparticles for cancer therapy

Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability. However, HSA/drug nanocomplexes have to experience complicated manufacturing process including multiple high-pressure homogenization and removing organic solvent under reduced pressure condition. Besides, the clinical application of these HSA/drug nanocomplexes is often limited because of their unsatisfactory stability and restricted dose. To overcome these issues, a redox-responsive paclitaxel-pentadecanoic acid prodrug conjugate embedded human serum albumin nanoparticles (NPs) was developed as a model in this report. First, PTX was activated and conjugated with 11-mercaptoundecanoic acid through a disulfide bond. The resultant disulfide bond bridged paclitaxel-pentadecanoic acid conjugate (PTX-SS-C10-COOH) was characterized by NMR and MS. After that, PTX-SS-C10-COOH dissolved in ethanol was mixed with HSA in water followed by lyophilization to generate HSA/PTX-SS-C10-COOH nanoparticles (HPTX NPs). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) characterization indicated that the HPTX NPs have spherical structure with an average diameter of approximately 120 nm. The formation of HSA/PTX-SS-C10-COOH NPs was confirmed by fluorescence quenching technology, ascribed to electrostatic and hydrophobic interactions. The HPTX NPs displayed a highdrug loading of 29.78 % and an entrapment efficiency of 94.16 %. Their reduced responsiveness was validated by glutathione (GSH)-triggered fast release of PTX. The pharmacokinetics, antitumor efficacy and systemic toxicity of HPTX NPs were thoroughly evaluated. The results showed that the HPTX NPs had longer retention, more effective tumor growth inhibition and lower toxicity compared with commercialized Taxol®. Importantly, the HPTX NPs could be administered at much high dose to achieve a significant tumor growth inhibition compared with Abraxane®. Together, the redox-responsive HPTX NPs with high drug loading is a promising strategy to deliver PTX for cancer chemotherapy.

Rapid generation of homogenous tumor spheroid microtissues in a scaffold-free platform for high-throughput screening of a novel combination nanomedicine.

Combination nanomedicine is a potent strategy for cancer treatment. Exploiting different mechanisms of action, a novel triple drug delivery system of 5-fluorouracil, curcumin, and piperine co-loaded human serum albumin nanoparticles (5FU-CUR-PIP-HSA-NPs) was developed via the self-assembly method for suppressing breast tumor. Both hydrophobic and hydrophilic drugs were successfully encapsulated in the HSA NPs with a high drug loading efficiency (DLE) of 10%. Successful clinical translation of nanomedicines, however, is a challenging process requiring considerable preclinical in vitro and in vivo animal tests. The aim of this study was to develop a homemade preclinical 3D culture model in the standard 96-well plates in a cost and time-effective novel approach for the rapid generation of homogenous compact tumor spheroids for disease modeling, and anticancer therapeutic/nanomedicine screening. The knowledge of drug screening can be enhanced by employing such a model in a high-throughput manner. Accordingly, to validate the formulated drug delivery system and investigate the cellular uptake and cytotoxicity effect of the nanoformulation, 3D tumor spheroids were employed. The practicality of the nanomedicine system was substantiated in different tests. The in vitro uptake of the NPs into the tight 3D tumor spheroids was facilitated by the semi-spherical shape of the NPs with a proper size and surface charge. 5FU-CUR-PIP-HSA-NPs demonstrated high potency of migration inhibition as a part of successful anti-metastatic therapy as well. The remarkable differences in 2D and 3D cytotoxicities emphasize the importance of employing 3D tumor models as an intermediate step prior to in vivo animal experiments for drug/nanomedicine screening.

Cisplatin and Albumin-Based Gold–Cisplatin Nanoparticles Enhance Ablative Radiation Therapy–Induced Antitumor Immunity in Local and Distant Tumor Microenvironment

Ablative radiation therapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity. The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au-cisplatin NPs. Combining ablative RT with cisplatin or Au-cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells, including natural killer T cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au-cisplatin NPs group. Cisplatin and Au-cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed unirradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector tumor-infiltrating immune cells including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au-cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect. Compared with cisplatin, the albumin-based Au-cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events and can be safely administered concurrently with ablative RT. Alternative NP formulations may be designed to further improve anticancer outcomes.