Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy.

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.

Use of surfactant-based amorphous solid dispersions for BDDCS class II drugs to enhance oral bioavailability: A case report of resveratrol.

This paper aimed to improve in vitro dissolution/solubility as well as inhibit intestinal metabolism and thus enhance oral bioavailability for a BDDCS class II drug by constructing surfactant-based amorphous solid dispersions using resveratrol (RES) as a model drug. After preliminary screening of polymers and surfactants, and subsequent prescription optimization, two optimized spray-drying RES-polymer-surfactant ASDs were obtained and exhibited a significant increase in solubility of RES by 2.69-3.45-fold compared to crystalline RES, and by 1.13-1.56-fold compared to corresponding RES-polymer ASDs, maintaining a higher concentration in the dissolution process. A metabolism study using everted sacs showed that two optimized ASDs reduced the concentration ratio of RES-G to RES to 51.66%-52.05% of crystalline RES on the serosal side of the rat everted intestinal sac at 2 h. Consequently, these two RES-polymer-surfactant ASDs achieved significantly higher exposure of RES in the plasma with significant enhancements in Cmax (2.33-2.35-fold higher than crystalline RES, and 1.72-2.04-fold higher than corresponding RES-polymer ASDs), and in AUC 0-∞ (3.51-3.56-fold higher than crystalline RES, and 1.38-1.41-fold higher than corresponding RES-polymer ASDs). These advantages of the RES-polymer-surfactant ASDs in oral absorption of RES were attributed to solubilization by ASDs and metabolic inhibition by UGT inhibitors. The introduction of surfactants including EL and Lab to ASDs plays an important role in inhibiting glucuronidation and further improving solubility. This study demonstrated that such surfactant-based amorphous solid dispersions may serve as a new approach to increase the oral absorption of BDDCS class II drugs.

Effects of topography and historical disturbance on canopy height structure of tropical forests in Menglun, Xishuangbanna, China.

With the combination of airborne Lidar and panchromatic images in 1981 and 2021, we investigated the canopy height structure of tropical forests in Menglun sub-reserve in the Xishuangbanna National Nature Reserve of Yunnan Province, and analyzed its relationship with environmental factors by using multiple regression tree (MRT) method. The results showed that forests in the Menglun sub-reserve could be clustered into seven types based on canopy height structures, with tropical rainforest, monsoon evergreen broad-leaved forest, secondary forest, and flood plain forest as the main types. The potential solar radiation, altitude, terrain profile curvature, slope and the brightness value of imageries in 1981 and 2021 were main factors that drove the classification. The tropical seasonal rainforest dominated by Pometia pinnata occupied the largest area in valley and low-land. The monsoon evergreen broad-leaved forest dominated by Castanopsis echinocarpa mainly distributed in the ridge and disturbed areas. The secondary forests had homogeneous canopy surface, which was significantly different from the primary forests. The activities of swidden agriculture about three decades ago had legacy impacts on the physiognomy of secondary forests.

Co-amorphous systems using epigallocatechin-3-gallate as a co-former: Stability, in vitro dissolution, in vivo bioavailability and underlying molecular mechanisms.

Co-amorphous strategy has been extensively investigated to improve the dissolution of hydrophobic drugs. Here, epigallocatechin-3-gallate (EGCG) was exploited as a co-former in co-amorphous systems based on its unique structure including phenyl rings, phenolic hydroxyl groups and the galloyl moiety. Two model BCS class II drugs, simvastatin (SIM) and nifedipine (NIF), were selected to be co-amorphized with EGCG. All drug-EGCG systems at three molar ratios became amorphous by the means of spray drying and showed high physically stable either under dry condition and 75 % RH at 40 °C or under dry conditions at 25 °C. The optimal feed molar ratios of both EGCG based co-amorphous systems fabricated were determined to be three, under which the significant increases were obtained in the maximum apparent concentrations of 4.90-fold for SIM at 1 h and 106.03-fold for NIF at 0.25 h compared to crystalline drugs by non-sink dissolution studies. The underlying molecular mechanisms of two co-amorphous systems formation were involved in molecular miscibility, hydrogen bonds and π-π stacking interactions unraveled by means of DSC, FTIR and molecular dynamics simulations. More to the point, oral pharmacokinetic studies in rats demonstrated that co-amorphous SIM-EGCG and NIF-EGCG systems at 1:3 have a significant increase in Cmax of 1.81- and 5.69-fold, and AUC 0-24h of 1.62- and 4.57-fold compared with those of corresponding crystalline drugs, respectively. In conclusion, EGCG is proved to be a promising co-former in co-amorphous systems.

Excipient-free nanodispersions dominated by amphiphilic glycosides for bioavailability enhancement of hydrophobic aglycones, a case of glycyrrhetinic acid with diammonium glycyrrhizinate.

Natural aglycones, a major ingredient accompanied by glycosides in plants, have played an important role in the treatment of various diseases. However, their bioavailability is limited by their poor water solubility. In contrast to previous efforts that required the use of new exotic materials which may raise concerns about biocompatibility, we report the first case of excipient-free nanodispersions in which an insoluble glycyrrhetinic acid (GA) assembled with its amphiphilic parent drug diammonium glycyrrhizinate (DG) into water-dispersible nanodispersions (130.8 nm for particle size and 91.74% for encapsulation efficiency). This strategy largely increased GA's water apparent solubility by hundreds of times to 549.0 µg/mL with a high cumulative dissolution percentage in vitro greater than 80% in 5 min. The study on the formation mechanism showed that the OH, C-O and C=O group stretching peaks shifted in the FTIR spectra of GA-DG nanodispersions, while the COOH peak (δ COOH 12.19 ppm) disappeared in the 1H NMR spectrum of GA-DG nanodispersions, indicating that carboxyl groups on GA may interact with the hydroxyl groups of DG in solution. Molecular dynamics simulations suggested that both hydrophobic interactions and hydrogen-bond interactions contribute to the coassembly of GA and DG molecules in aqueous solution. Oral pharmacokinetic studies in rats demonstrated that such nanodispersions have a significant increase in Cmax and AUC0-t of 2.45- and 3.45-fold compared with those for GA, respectively. Therefore, this strategy, employing amphiphilic glycosides as excipients to prepare nanodispersions, not using new materials, paves the way for the further application of hydrophobic aglycone drugs.

Lipoprotein-biomimetic nanostructure enables tumor-targeted penetration delivery for enhanced photo-gene therapy towards glioma.

Glioma is one of the most malignant primary tumors affecting the brain. The efficacy of therapeutics for glioma is seriously compromised by the restriction of blood-brain barrier (BBB), interstitial tumor pressure of resistance to chemotherapy/radiation, and the inevitable damage to normal brain tissues. Inspired by the natural structure and properties of high-density lipoprotein (HDL), a tumor-penetrating lipoprotein was prepared by the fusion tLyP-1 to apolipoprotein A-I-mimicking peptides (D4F), together with indocyanine green (ICG) incorporation and lipophilic small interfering RNA targeted HIF-1α (siHIF) surface anchor for site-specific photo-gene therapy. tLyP-1 peptide is fused to HDL-surface to facilitate BBB permeability, tumor-homing capacity and -site accumulation of photosensitizer and siRNA. Upon NIR light irradiation, ICG not only served as real-time targeted imaging agent, but also provided toxic reactive oxygen species and local hyperthermia for glioma phototherapy. The HIF-1α siRNA in this nanoplatform downregulated the hypoxia-induced HIF-1α level in tumor microenvironment and enhanced the photodynamic therapy against glioma. These studies demonstrated that the nanoparticles could not only efficiently across BBB and carry the payloads to orthotopic glioma, but also modulate tumor microenvironment, thereby inhibiting tumor growth with biosafety. Overall, this study develops a new multifunctional drug delivery system for glioma theranostic, providing deeper insights into orthotopic brain tumor imaging and treatment.

Extra virgin olive oil-based phospholipid complex/self-microemulsion enhances oral absorption of salvianolic acid B through inhibition of catechol-O-methyltransferase-mediated metabolism.

The oral bioavailability of many phenolic acid drugs is severely limited due to the high hydrophilicity and extensive first-pass effect induced by catechol-O-methyltransferase (COMT) metabolism. The present study investigated the inhibitory activity of the pharmaceutical excipients of extra virgin olive oil (EVOO) against COMT and evaluated the potential of a self-microemulsion loaded with a phospholipid complex containing EVOO for oral absorption enhancement of salvianolic acid B (SAB), a model phenolic acid. In vitro COMT assay showed that EVOO could effectively inhibit enzyme activity in the rat liver cytosol. Next, the SAB phospholipid complex/self-microemulsion containing EVOO (named SP-SME1) was prepared and characterized (particle size, 243.60 ± 6.96 nm and zeta potential, -23.67 ± -1.36 mV). The phospholipid complex/self-microemulsion containing ethyl oleate (EO) (named SP-SME2) was taken as the control group. Compared with free SAB, the apparent permeability coefficient (Papp value) of the two SP-SMEs significantly increased (12.0-fold and 10.90-fold). Pharmacokinetic study demonstrated that the AUC0-∞ value of SAB for the SP-SME1 group significantly increased by 4.72 and 2.82 times compared to those for free SAB (p < 0.001) and SP-SME2 (p < 0.01), respectively. Moreover, the AUC0-∞ value of monomethyl-SAB (metabolite of SAB, MMS) for the SP-SME1 group decreased by 0.83 times compared to that for SP-SME2. In conclusion, the EVOO-based phospholipid complex/self-microemulsion greatly enhanced the oral absorption of SAB, which was mainly attributed to the inhibition of COMT activity induced by EVOO.

Emerging prospects of extracellular vesicles for brain disease theranostics.

In the past decade, bio-nanoparticles inspired by nature with advantageous properties have attracted extensive interest for accurate diagnosis and effective treatment. Extracellular vesicles (EVs) are nanosized naturally derived vesicles which contain a variety of bioactive molecules reflecting their cell of origin. Emerging advances in the field of EV nanotechnology bring along novel promises for blooming the development of EV-based therapeutics. Studies of the EV features in central nervous system physiology and brain disease pathology explosively promote the idea of harnessing these endogenous vesicles as a promising strategy for brain disease theranostics. These nanosized vesicles with natural blood-brain barrier-crossability, remarkable physicochemical properties and excellent biocompatibility are considered a prime candidate as an intelligent vehicle for brain therapeutic and drug delivery applications. Here, this review provides an overview on the characteristics, isolation and internalization of EVs, and the recent progresses in the strategies and methodologies of modified EVs for effective cargo-loading is presented. The potential theranostics applications of EVs in brain diseases are further discussed by presenting representative examples. The challenges and obstacles of current studies are also presented, and perspectives for successful clinical translation are further discussed.

Shoot base responds to root-applied glutathione and functions as a critical region to inhibit cadmium translocation from the roots to shoots in oilseed rape (Brassica napus).

Glutathione (GSH) is a tripeptide involved in controlling heavy metal movement in plants. Our previous study showed that GSH, when site-specifically applied to plant roots, inhibits Cd translocation from the roots to shoots in hydroponically cultured oilseed rape (Brassica napus) plants. A factor that led to this inhibitory effect was the activation of Cd efflux from root cells. To further investigate the molecular mechanism triggered by root-applied GSH, Cd movement was non-invasively monitored using a positron-emitting tracer imaging system. The Cd absorption and efflux process in the roots were visualized successfully. The effects of GSH on Cd efflux from root cells were estimated by analyzing imaging data. Reanalysis of image data suggested that GSH applied to roots, at the shoot base, activated Cd return. Cutting the shoot base significantly inhibited Cd efflux from root cells. These experimental results demonstrate that the shoot base plays an important role in distributing Cd throughout the plant body. Furthermore, microarray analysis revealed that about 400 genes in the roots responded to root-applied GSH. Among these, there were genes for transporter proteins related to heavy metal movement in plants and proteins involved in the structure modification of cell walls.

Improved efficacy of Panax notoginseng saponin loaded into BSP/alginate microspheres for the treatment of alcoholic gastric ulcers.

Previously, we have reported the evaluations of alginate and Bletilla striata polysaccharide (BSP) in formulation of microsphere, which is a muco-adhesive carrier and can achieve a long duration of gastric retention. The combination of Panax notoginseng (Burk.) and B. striata is a traditional Chinese herbal formula that is used to treat gastric ulcers. BSP, an effective ingredient of B. striata, possesses both medicinal and excipient functions. Panax notoginseng saponin (PNS), which can easily dissolve in water, is the main effective ingredient in P. notoginseng (Burk.) for the treatment of gastric ulcers. However, microspheres containing PNS could directly cause drug leakage, ultimately reducing the encapsulation rate. In this study, PNS was fabricated into a hydrophobic dispersion with slow-release characteristics. Subsequently, PNS was packaged into BSP/alginate microspheres to improve the encapsulation rate. The prepared PNS-loaded microspheres were round, the release characteristics aligned with the Weibull equation, and the active ingredients were released by diffusion and erosion. The developed microspheres improved the effects of PNS and synergistically exerted the pharmaceutical effects of BSP on acute gastric ulcers.

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen).

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Mucoadhesive nanocrystal-in-microspheres with high drug loading capacity for bioavailability enhancement of silybin.

Nanocrystals, due to high drug loading efficiency, have drawn large attention as nanotechnology to enhance solubility and bioavailability of poorly soluble drugs. However, most nanocrystals still encountered low oral absorption percentage due to its insufficient retention time in the gastrointestinal tract (GI). In this work, silybin (SB) as model drug was fabricated to nanocrystals, and further loaded into a mucoadhesive microsphere to increase the GI retention. Such mucoadhesive microspheres were prepared with a wet media milling technique followed by coagulation and film coating. Nanocrystals and microspheres were thoroughly characterized by diverse complementary techniques. As results, such delivery system displayed an encapsulation efficiency of approximately 100 % and a drug loading capacity of up to 35.41 ± 0.31 %. In addition, mucoadhesiveness test ex vivo conducted with rat intestine showed that film-coated microspheres were retained for more than 1 h. Benefiting from nanocrystals technology, the drug cumulative release percentage of the microspheres was remarkable improved compared to unprocessed one in vitro. Finally, pharmacokinetics studies in rats showed a significant 3-fold increase of drug oral bioavailability compared to unprocessed SB. The current study demonstrates that the developed delivery vehicle can enhance the bioavailability of SB by increasing its dissolution percentage as well as through extending retention time in the GI tract, and achieve high drug loading capacity.

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions.

BACKGROUND: The management of metastatic cancer remains a major challenge in cancer therapy worldwide. The targeted delivery of chemotherapeutic drugs through rationally designed formulations is one potential therapeutic option. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules have been evaluated as promising candidates for the next generation of drug formulations. Formulated from the self-assembly of drug molecules, these nanodispersions enable the safe and effective delivery of therapeutic drugs to local disease lesions. Here, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with the interaction force and did not involve any organic solvents. RESULTS: According to molecular dynamics (MD) simulations, DOX molecules tend to assemble around RHE molecules through intermolecular forces. This intermolecular retention of DOX was further improved by the nanosizing effect of RD NPs. Compared to free DOX, RD NPs exerted a slightly stronger inhibitory effect on 4T1 cells in the scratch healing assay. As a dual drug-loaded nanoformulation, the efficacy of RD NPs against tumor cells in vitro was synergistically enhanced. Compared to free DOX, the combination of DOX and RHE in nanoparticles exerted a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis. Furthermore, the RD NP treatment not only effectively suppressed primary tumor growth but also significantly inhibited tumor metastasis both in vitro and in vivo, with a better safety profile. CONCLUSIONS: The generation of pure nanodrugs via a self-assembly approach might hold promise for the development of more efficient and novel excipient-free nanodispersions, particularly for two small molecular antitumor drugs that potentially exert synergistic antiproliferative effects on metastatic breast cancer.

Impacts of particle size on the cytotoxicity, cellular internalization, pharmacokinetics and biodistribution of betulinic acid nanosuspensions in combined chemotherapy.

To evaluate the effect of particle size on the cellular internalization, tissue distribution, and bioavailability of betulinic acid nanosuspensions (BA/NSs) and further investigate the combined effect of BA/NSs and Taxol® on breast cancer, BA/NSs with different particle sizes (160 nm, 400 nm, and 700 nm) were prepared by an efficient universal green technology. The use of BA/NS (160 nm) was more likely to increase the BA release rate and enhance bioavailability compared with the use of larger size particles. BA/NSs were internalized by 4T1 cells in different ways, including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. For the 4T1 orthotopic tumor model, BA/NS (160 nm) showed a tendency to accumulate at a higher level in tumor tissue. Moreover, combination therapy with BA/NSs and Taxol® showed remarkable potential to enhance antitumor activity in vitro and in vivo. The cytotoxicity and apoptotic ability of the different preparations decreased in the following order: BA/NS (160 nm) + Taxol®, BA/NS (400 nm) + Taxol®, and BA/NS (700 nm) + Taxol®. The tumor inhibition rates of BA/NSs (160 nm, 400 nm, and 700 nm) combined with Taxol® were 2.35-, 1.74- and 1.12-fold higher than that of free BA, respectively. The combined chemotherapy showed good safety, indicating that it had the effect of enhancing treatment and reducing toxicity.

Resource, chemical structure and activity of natural polysaccharides against alcoholic liver damages.

Many natural polysaccharides from bio-resources hold advantages of multi-functions, high efficiency, non-toxicity or low side effect, and have strong potentials in protection against alcoholic liver damages. This review summarized the bio-resources, chemical and structural characteristics of natural polysaccharides with potentials in inhibition against alcoholic liver damages, and also emphasized knowledge on correlations between their chemical structure and function. Approximately 95 species were confirmed in generation of hepatoprotective polysaccharides. Products as crude polysaccharides originated from 17 species were sum up despite the indetermination of their accurate structure. Additional four polysaccharides were described for their known chemical structures. Possible roles of hepatoprotective polysaccharides were provided with evidence on antioxidant promotion, lipids regulation, apoptosis inhibition and anti-inflammation, as well as confirmations in immune enhancement, iron removal and anti-fibrosis when currently treated against the alcoholic liver damages. To sum up, this overview could serve to guide development and utilization of natural hepatoprotective polysaccharides.

Mucoadhesive improvement of alginate microspheres as potential gastroretentive delivery carrier by blending with Bletilla striata polysaccharide.

As polysaccharide from Bletilla striata (BSP) was anticipated with mucoadhesive improvement in sodium alginate (SA) microspheres, BSP was mixed with SA to construct a composite microsphere to retain in the gastrointestinal tract for a long time. The morphological properties, particle size and thermodynamic properties of the microspheres in combination with comprehensive evaluations in the swelling properties, mucin adsorption, ex vivo and in vivo gastric retention were determined to characterize the mucoadhesion of SA-BSP blend microspheres. Results showed that the prepared microspheres were discrete and spherical. The addition of BSP increased flexibility and reduced rigidity of SA microsphere. Furthermore, the swelling property, mucin adsorption ability and the retention rate on the gastric mucosa of SA matrix were increased after blending with BSP. Mucoadhesion tests showed the SA-BSP microspheres stayed much longer in rats' stomach than the SA microsphere did. Above all, the SA-BSP microspheres with the enhanced mucoadhesion suggested being a potential drug carrier in developing the gastroretentive drug delivery system.

Effects of the preparation method of Pt/g-C3N4 photocatalysts on their efficiency for visible-light hydrogen production.

As a two-dimensional (2D) nanomaterial, bulk g-C3N4 (CNB) has a low specific surface area and weak electron transport ability, which limit its application in photocatalysis. In this paper, ultrathin porous g-C3N4 nanosheets (CNS) have been synthesized by thermal oxidation etching of CNB. Compared with CNB, CNS possess a larger surface area of 234.65 m2 g-1, good dispersity in water and a high electron transfer rate. As a co-catalyst, ultra-small Pt nanoparticles (NPs) with high dispersity are successfully loaded on the surface of CNS. It is found that changing the loading method of Pt NPs in the preparation step remarkably alters the efficiency for hydrogen production. The Pt/CNS-CR photocatalyst fabricated by the chemical reduction (CR) method shows a much higher efficiency for H2 evolution from water splitting, compared to the Pt/CNS-PR photocatalyst obtained by the loading of Pt NPs by the traditional photo-reduction (PR) method. When triethanolamine (TEOA) is used as a hole sacrificial agent, the hydrogen production rate of 2.0%-Pt/CNS-CR is 7862.5 µmol g-1 h-1, which is 6.92 times higher than that of 2.0%-Pt/CNS-PR (1136.8 µmol g-1 h-1). The valence states of the Pt element in the Pt/CNS-CR and Pt/CNS-PR nanocomposites have been analyzed by X-ray photoelectron spectroscopy, respectively. At the same time, the effects of the loading amount of Pt and different sacrificial reagents on the photocatalytic H2 generation activity have also been systematically investigated.

Laser-triggered polymeric lipoproteins for precision tumor penetrating theranostics.

Natural particles ranging from various cell membranes to nascent proteins are highly optimized for their specific functions in vivo and possess features that are desired in drug delivery carriers. However, the current endeavor in research on bioparticles is still seeking the appropriate strategy to shield multiple agents and circumvent biological hurdles. These issues have propelled the advancement of lipid-polymer hybrid nanocarriers, which could be employed as drug reservoirs and strive to meet these expectations. We thereby proposed functionalized biopeptide-lipid hybrid particles, which were applied to encapsulating a PLGA polymeric core together with indocyanine green (ICG) and packaged by a lipoprotein-inspired structural shell. To initiate precision tumor-penetrating performance, tLyP-1-fused apolipoprotein A-I-mimicking peptides (D4F) were exploited to impart tumor-homing and tumor-penetrating biological functions. The sub-100 nm drug vehicle possessed a long circulation time with uniform mono-dispersity but was stable enough to navigate freely, penetrate deeply into tumors and deliver its cargoes to the targeted sites. Moreover, ICG-encapsulated penetrable polymeric lipoprotein particles (PPL/ICG) could realize real-time fluorescence/photoacoustic imaging for monitoring in vivo dynamic distribution. Upon near-infrared (NIR) laser irradiation, PPL/ICG demonstrated a highly efficient phototherapeutic effect to eradicate orthotopic xenografted tumors, resulting in an 88.77% decrease from the initial tumor volume and inhibited tumor metastasis with good biosafety. Therefore, the described bio-strategy opens new avenues for creating polymeric lipoproteins with varied hybrid functionalities, which may be applied to provide a basis and inspiration for improved nanoparticle-based precision theranostic nanoplatforms.

Enhanced anti-colon cancer efficacy of 5-fluorouracil by epigallocatechin-3- gallate co-loaded in wheat germ agglutinin-conjugated nanoparticles.

Colon adenocarcinoma is the third most common cause of cancer-related deaths worldwide owing to its aggressive nature. Here, we developed a novel oral drug delivery system (DDS) that comprised active targeted nanoparticles made from gelatin and chitosan (non-toxic polymers). The nanoparticles were fabricated using a complex coacervation method, which was accompanied by conjugation of wheat germ agglutinin (WGA) onto their surface by glutaraldehyde cross-linking. Specifically, we integrated 5-fluorouracil (5-FU), the first-line treatment agent against colon cancer, and (-)-epigallocatechin-3-gallate (EGCG), which inhibits tumor growth via anti-angiogenesis and apoptosis-inducing effects, into the nanoparticles, named WGA-EF-NP. The 5-FU and EGCG co-loaded nanoparticles showed sustained drug release, enhanced cellular uptake, and longer circulation time. WGA-EF-NP exhibited superior anti-tumor activity and pro-apoptotic efficacy compared to the drugs and nanoparticles without WGA decoration owing to better bioavailability and longer circulation time in vivo. Thus, WGA-EF-NP shows promise as a DDS for enhanced efficacy against colon cancer.

Treatment of metastatic lung cancer via inhalation administration of curcumin composite particles based on mesoporous silica.

Curcumin attracted attention due to its promising anti-cancer properties and safety performance. However, its poor aqueous solubility and low bioavailability have to be overcome before it goes into clinic use. Here, porous composite particles are prepared by loading curcumin into mesoporous material SBA-15, and its therapeutic effect on lung cancer via inhalation administration have also been evaluated. The inclusion of curcumin in host material SBA-15 was confirmed by the reduced surface area and pore diameter of the composite material, and the aerodynamic performance of the composite material was investigated by FT-4 and NGI. Phagocytosis experiments on RAW264.7, the toxicity of material extracts on BEAS-2B cells, and the haemolysis experiments showed that the mesoporous materials had good biocompatibility at 10-400 µg/mL. The B16F10 melanoma metastatic lung mouse model was used to investigate the therapeutic effect of lung cancer after inhalable administration. It was found that the body weight of the curcumin composite particle-administered group decreased more slowly and the lung disease developed slower than the curcumin crude drug group, indicating that the composite particles has a certain inhibitory effect on tumours.