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The carrier-free chemo-photothermal therapy has become a promising strategy to improve anti-cancer therapeutic efficacy owing to the combination of chemotherapy and photothermal therapy, with improved chemotherapy drug pharmacodynamics and pharmacokinetics, high drug loading, and reduced toxicity. We designed a novel carrier-free targeting nanoparticles, co-self-assembled amphiphilic prodrugs 3′,5′-dioleoyl gemcitabine (DOG), and tumor-targeted γ-octadecyl folate (MOFA), with encapsulated US Food and Drug Administration (FDA)-approved photosensitizer indocyanine green (ICG) for synergistic chemo-photothermal therapy. The DOG linking oleic acid to the sugar moiety of gemcitabine (GEM) showed better self-assembly ability among GEM amphiphilic prodrugs linking different fatty acids. The readily available and highly reproducible 3′,5′-dioleoyl gemcitabine/γ-octadecyl folate/indocyanine green (DOG/MOFA/ICG) nanoparticles were prepared by reprecipitation and showed nano-scale structure with mono-dispersity, great encapsulation efficiency of ICG (approximately 74%), acid- and laser irradiation-triggered GEM release in vitro and sustained GEM release in vivo after intravenous administration as well as excellent temperature conversion (57.0°C) with near-infrared laser irradiation. The combinational DOG/MOFA/ICG nanoparticles with near-infrared laser irradiation showed better anti-tumor efficacy than individual chemotherapy or photothermal therapy, with very low hemolysis and inappreciable toxicity for L929 cells. This co-self-assembly of the ICG and the chemotherapy drug (GEM) provides a novel tactic for the rational design of multifunctional nanosystems for targeting drug delivery and theranostics.

A tumor‐targeting enhanced chemotherapy, enabled by aptamer‐drug conjugate nanomicelles, is reported that boosts antitumor immune responses. Multivalent aptamer drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of a hydrophilic aptamer and a hydrophobic monodendron anchored with four anticancer drugs by acid‐labile linkers, was designed and synthesized. By co‐self‐assembly with an ApMDC analogue, in which aptamer is replaced with polyethylene glycol, the surface aptamer density of these nanomicelles can be screened to reach an optimal complementation between blood circulation and tumor‐targeting ability. Optimized nanomicelles can enhance immunogenic cell death of tumor cells, which strikingly augments the tumor‐specific immune responses of the checkpoint blockade in immunocompetent tumor‐bearing mice. ApMDC nanomicelles represent a robust platform for structure–function optimization of drug conjugates and nanomedicines. [ABSTRACT FROM AUTHOR]

Co-self-assembly of lignin oligomers together with other structurally similar molecules can provide composite particles with functional properties for specific applications. Herein, tannin was co-self-assembled for the first time with lignin oligomers into novel lignin–tannin particles (L x T y), induced by a dual driven force with π–π stacking interaction and hydrogen bonds. Abundant ortho -phenolic hydroxyl groups of tannin cause the efficient adsorption and partial reduction of Pd2+ ions (36.7%) by L x T y (>99%) to obtain Pd/L x T y with highly dispersed Pd nanoparticles, thereby avoiding the need for surfactants or reducing agents. Aldehyde groups of lignin-derived aldehydes could preferentially interact with phenolic hydroxyl groups on the hydrophilic shell of Pd/L x T y. Then, mitigated active hydrogen atoms on the L x T y support during the hydrogen spillover process induced a H-shift to C of −C O through a water bridge with low energy barrier and consequently selective hydrogenation to obtain lignin-derived alcohols at 30 °C. [Display omitted] • Biomass-based lignin and tannin exhibited excellent co-assembly ability. • L x T y was used as supports for the in-situ synthesis of Pd/L x T y catalysts. • Pd/L x T y -catalyzed selective hydrogenation of lignin-derived aldehydes into alcohols. • Strong hydrogen spillover properties of Pd/L x T y improved its catalytic selectivity. [ABSTRACT FROM AUTHOR]

The carrier-free chemo-photothermal therapy has become a promising strategy to improve anti-cancer therapeutic efficacy owing to the combination of chemotherapy and photothermal therapy, with improved chemotherapy drug pharmacodynamics and pharmacokinetics, high drug loading, and reduced toxicity. We designed a novel carrier-free targeting nanoparticles, co-self-assembled amphiphilic prodrugs 3',5'-dioleoyl gemcitabine (DOG), and tumor-targeted γ-octadecyl folate (MOFA), with encapsulated US Food and Drug Administration (FDA)-approved photosensitizer indocyanine green (ICG) for synergistic chemo-photothermal therapy. The DOG linking oleic acid to the sugar moiety of gemcitabine (GEM) showed better self-assembly ability among GEM amphiphilic prodrugs linking different fatty acids. The readily available and highly reproducible 3',5'-dioleoyl gemcitabine/γ-octadecyl folate/indocyanine green (DOG/MOFA/ICG) nanoparticles were prepared by reprecipitation and showed nano-scale structure with mono-dispersity, great encapsulation efficiency of ICG (approximately 74%), acid- and laser irradiation-triggered GEM release in vitro and sustained GEM release in vivo after intravenous administration as well as excellent temperature conversion (57.0°C) with near-infrared laser irradiation. The combinational DOG/MOFA/ICG nanoparticles with near-infrared laser irradiation showed better anti-tumor efficacy than individual chemotherapy or photothermal therapy, with very low hemolysis and inappreciable toxicity for L929 cells. This co-self-assembly of the ICG and the chemotherapy drug (GEM) provides a novel tactic for the rational design of multifunctional nanosystems for targeting drug delivery and theranostics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuang, Liu, Wang, Yang, Zeng and Ming.)

Abstract: Carbon‐based nanomaterials could afford versatile potential applications in biomedical optical imaging and as nanoparticle drug carriers, owing to their promising optical and biocompatible capabilities. In this paper, it is first found that amphipathic cetylpyridinium chloride (CPC)‐stabilized oil‐soluble carbon dots (CDs) could self‐assemble into hydrophilic CDs clusters with hydrophobic core under ultrasound, in which CPC acts as carbon source, stabilizer, and phase transfer agent. Next, the size‐control (for size‐dependent passive tumor targeting) and doxorubicin (DOX) uploading of aqueous CDs clusters, and subsequent surface charge modification via overcoating with cRGD‐ and octylamine‐modified polyacrylic acid (cRGD‐PAA‐OA) (reversing their surface charges into negative and introducing active tumor‐targeting ability) are explored systematically. Based on this sequential administration mode, CDs‐cluster‐DOX/cRGD‐PAA‐OA nanocomposites exhibit selective human malignant glioma cell line (U87MG) tumor targeting. In in vitro drug release experiments, the nanocomposites could release DOX timely. Owning to the dual tumor targeting effects and seasonable drug release, CDs‐cluster‐DOX/cRGD‐PAA‐OA show remarkably tumor targetability and enhanced antitumor efficacy (and reduced adverse reaction), comparing to free DOX in animal models. These results indicate that fabricating nanocomposite via co‐self‐assembly strategy is efficient toward drug delivery system for tumor‐targeting theranostic. [ABSTRACT FROM AUTHOR]

Multimodal imaging-guided synergistic combination therapy has shown great potential for cancer treatment. However, the nanocarrier-based theranostic systems suffer from batch-to-batch variation, complexity of multicomponent, poor drug loading, and carrier-related toxicity issues. To address these issues, herein we developed a novel carrier-free theranostic system with nanoscale characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular nanoparticles (NPs) in aqueous solution without any molecular precursor or excipient via collaborative interactions (electrostatic, π–π stacking, and hydrophobic interactions). The exceptionally high dual-drug loading (∼ 92 wt%) ICG-EPI NPs showed good physiological stability, preferable photothermal response, excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior, and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in comparison with individual chemotherapy or PTT, the combinational chemo-PTT therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced apoptosis and death of cancer cells in vitro , and showed synergistic chemo-PTT efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore, the ICG-EPI NPs exhibited inappreciable toxicity. This co-self-assembly of both FDA-approved agents provides a safe and “Molecular economical” strategy in the rational design of multifunctional nano-theranostic systems for real-time self-monitoring intracellular drug delivery and targeting multimodal imaging-guided synergistic combination therapy. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticle-containing capsules have been proposed for many uses, including triggered drug delivery and imaging. Combining superparamagnetic iron oxide nanoparticles (SPIONs) with existing liposome drug delivery technology is an enticing near-future prospect, but it requires efficient methods of synthesis and formulation compatible with pharmaceutical applications. We report a facile way of producing large, unilamellar, and homogeneously sized magnetoliposomes with high content of monodisperse, hydrophobic SPIONs integrated in the lipid membrane by use of a solvent inversion technique. For low lipid concentrations, unilamellar and monodisperse vesicles were obtained that became increasingly multilamellar with higher lipid fraction. Both, the co-self-assembled structure and loading content were significantly influenced by the purity of the nanoparticle shell. SPIONs with homogeneous shells of nitrodopamine-anchored hydrophobic dispersants could be quantitatively loaded up to 20%w/w, while SPIONs also containing residual physisorbed oleic acid exhibited a loading cut-off around 10%w/w SPIONs accompanied by drastic changes in size distribution. Lipid acyl chain length crucially influenced the formation and resultant stability of the loaded assemblies. The formation of nanoparticle-loaded vesicles is exemplified in different biologically important media, yielding ready-to-use magnetoliposome formulations. [ABSTRACT FROM AUTHOR]

• A nanocluster-based frameworks was developed by dynamic combinatorial chemistry. • CA-NBF hazard-freely suppressed the Wnt/β-catenin signaling cascade. • CA-NBF selectively accumulated in solid tumors. • CA-NBF augmented the anti-cancer immunity. • 1These authors contributed equally. Tumor immunotherapy by PD-1/PD-L1 blockade (PPB) has emerged as a standard of care treatment and can bring long-lasting clinical benefits, yet less than one-third of patients respond to it. While combination PPB therapies have shown improved outcomes, more optimal multimodality therapies, particularly those combinations with molecularly targeted therapies, are still required to improve the therapeutic benefit of PPB. Herein, we describe a design of PPB sensitizer with supramolecular nanostructure constructed through a dynamic combinatorial chemistry (DCC)-based co-self-assembled strategy. Upon the stimulation of a β-catenin inhibitor termed carnosic acid (CA), two competing molecular blocks three-dimensionally and orderly co-self-assembled into a nanocluster-based framework (CA-NBF) under thermo-dynamic control. With properties of tumor-specific accumulation and glutathione-triggered release, CA-NBF potently suppressed the Wnt/β-catenin signaling cascade in vitro and in vivo , while keeping a favorable safety feature. Moreover, CA-NBF potently restored the intratumoral infiltration of cytotoxic T lymphocyte cells and consequently promoted tumor response to Anti-PD-L1 antibody in B16F10 melanoma model and Anti-PD1 antibody in MC38 model of colon cancer. Given these encouraging results, this work may provide a new option for promoting the response of PPB therapy, and the DCC-based co-self-assembled strategy may be a promising tool to develop a class of supramolecular nanomedicines for the molecular targeted therapy of diseases including cancer. [ABSTRACT FROM AUTHOR]

Nanomedicine-based phototherapy in combination with immune checkpoint blockade therapy has been reported as a promising strategy for improved cancer immunotherapy. However, tumor penetration of nanomedicine into solid tumor is still an unresolved obstacle to an effective drug delivery, leading to limitations in their applications. Here, we developed a tumor microenvironment-responsive prodrug nanoplatform for efficient penetration and photo-immunotherapy of cancer. The prodrug nanoplatform is performed by integrating PEGylated indoleamine-2,3-dioxygenase (IDO) inhibitor (Epacadostat) and photosensitizer (Indocyanine green, ICG) into a core-shell nanostructure via intermolecular interactions, which can transform into small dual-drug complexes (<40 nm) at tumor microenvironment. The resulting small dual-drug complexes could undergo caveolae-mediated endocytosis, enhance cellular uptake, directly kill tumor cells, in situ trigger antitumor immune response and modulate IDO-mediated immunosuppression. More significantly, the prodrug nanoplatform in combination with PD-L1 checkpoint blockade synergistically promoted the antitumor immunity and efficiently inhibited the growth of both primary and abscopal tumors. The present study provides a novel delivery strategy for nanoenabled phototherapy and IDO inhibition to combine PD-L1 checkpoint blockade for achieving more effective therapy of solid tumors. Image 1 [ABSTRACT FROM AUTHOR]