The development of nanomedicine formulations
to overcome the disadvantages
of traditional chemotherapeutic drugs and integrate cooperative theranostic
modes still remains challenging. Herein, we report the facile construction
of a multifunctional theranostic nanoplatform based on doxorubicin
(DOX)-loaded tannic acid (TA)–iron (Fe) networks (for short,
TAF) coated with fibronectin (FN) for combination tumor chemo-/chemodynamic/immune
therapy under the guidance of magnetic resonance (MR) imaging. We
show that the DOX-TAF@FN nanocomplexes created through in
situ coordination of TA and Fe(III) and physical coating
with FN have a mean particle size of 45.0 nm, are stable, and can
release both DOX and Fe in a pH-dependent manner. Due to the coexistence
of the TAF network and DOX, significant immunogenic cell death can
be caused through enhanced ferroptosis of cancer cells via cooperative
Fe-based chemodynamic therapy and DOX chemotherapy. Through further
treatment with programmed cell death ligand 1 antibody for an immune
checkpoint blockade, the tumor treatment efficacy and the associated
immune response can be further enhanced. Meanwhile, with FN-mediated
targeting, the DOX-TAF@FN platform can specifically target tumor cells
with high expression of αvβ3 integrin.
Finally, the TAF network also enables the DOX-TAF@FN to have an r
1 relaxivity of 6.1 mM–1 s–1 for T
1-weighted MR imaging
of tumors. The developed DOX-TAF@FN nanocomplexes may represent an
updated multifunctional nanosystem with simple compositions for cooperative
MR imaging-guided targeted chemo-/chemodynamic/immune therapy of tumors.
Scheme 1. A) Schematic illustration of the preparation of GCT@CM NPs. B) Cooperative tumor suppression through GCT@CM NP-mediated chemotherapy and PD-L1 blockade for enhanced tumor immunotherapy.
Amplification of endoplasmic reticulum stress (ERS) to realize enhanced cancer therapy has been considered to be unique in current cancer nanomedicine design. Herein, the design of metal–phenolic‐network‐coated dendrimer–drug conjugates as a novel theranostic nanoplatform based on ERS amplification is reported. In the design, acetylated generation‐5 poly(amidoamine) dendrimers are conjugated with an ERS drug, toyocamycin (Toy), through the attached phenylboronic acid moiety, and coated with an iron (Fe)–tannic acid (TF) network. The generated nanocomplexes with a size of 50.2 nm are stable under the physiological environment, and can rapidly release Toy under the tumor microenvironment due to the pH‐ and reactive‐oxygen‐species‐responsive boronic ester bonds to effectively inhibit the ERS‐mediated cancer cell adaptation. Meanwhile, the coated TF network enables the nanocomplexes to generate cytotoxic hydroxyl radicals through a Fenton reaction, amplifying the ERS for improved chemo/chemodynamic therapy of cancer cells in vitro and a xenografted breast tumor model in vivo. Moreover, the coating of TF also renders the complexes with an eminent r1 relaxivity for in vivo T1‐weighted tumor magnetic resonance imaging. The created intelligent nanocomplexes may represent an advanced nanomedicine formulation uniquely integrated with a metal–phenolic network and dendrimer nanotechnology for imaging‐guided cancer therapy through ERS amplification.
Summary
With the latent heat, the phase change material (PCM) is widely used in battery thermal management (BTM) to control the temperature. In this paper, the porous medium is employed to enhance the heat transfer of PCM. The lattice Boltzmann model for PCM/porous medium in pore scale is considered, where the mesh system with porous medium (fixed point) is generated by quartet structure generation set (QSGS) method. The effects of the Rayleigh number and porosity on the heat transfer process in BTM are investigated. The results show that decreasing the porosity will accelerate the melting rate. When the porosities are 0.9, 0.8, 0.7, and 0.6, the total melting times are decreased by 23.7%, 43.3%, 58.0%, and 75.4%, compared with pure PCM. The heat is transferred through the high‐conductivity framework. The natural convection in the porous medium is weak, and the conduction is the dominated heat transfer. As a result, the area of solid–liquid interface will be increased, and the heat‐transferred rate is accelerated. However, when the Rayleigh number is raised to 105, applying the porous medium with porosity of 0.9 will increase the total melting time, resulted from the stronger natural convection of PCM. The present study is helpful for design of PCM/porous medium‐based BTM.
Designing
intelligent stimuli-responsive nanoplatforms that are
integrated with a biological membrane system and nanomaterials to
realize efficient imaging and therapy of tumors still remains to be
challenging. Herein, we report a unique strategy to prepare redox-responsive
yellow fluorescent carbon dot nanoclusters (y-CDCs) loaded with anticancer
drug doxorubicin (DOX) and coated with the cancer cell membrane (CCM)
for precision fluorescence imaging and homologous targeting chemotherapy
of tumors. The y-CDs with a size of 7.2 nm were first synthesized via a hydrothermal method and crosslinked to obtain redox-responsive
y-CDCs with a size of 150.0 nm. The formulated y-CDCs were physically
loaded with DOX with an efficiency of up to 81.0% and coated with
CCM to endow them with antifouling properties, immune escape ability
to escape from macrophage uptake, and homologous targeting capability
to cancer cells. Within the reductive tumor microenvironment, the
y-CDCs with quenched fluorescence can dissociate to form single y-CDs
with recovered fluorescence and improved tumor penetration ability
and simultaneously release DOX from the “cluster bomb”,
thus realizing efficient targeted tumor fluorescence imaging and chemotherapy.
The designed y-CDCs/DOX@CCM may represent an updated nanomedicine
formulation based on CDs for improved theranostics of different types
of tumors.
Design of effective nanomedicines to modulate multiple immune cells to overcome the immune‐suppressive tumor microenvironment is desirable to improve the overall poor clinical outcomes of immunotherapy. Herein, a nanomedicine platform is reported based on chemotherapeutic drug doxorubicin (DOX)‐loaded phosphorus dendron micelles (M‐G1‐TBPNa@DOX, TBP, tyramine bearing two dimethylphosphonate) with inherent immunomodulatory activity for synergistic tumor chemoimmunotherapy. The M‐G1‐TBPNa@DOX micelles with good stability and a mean particle size of 86.4 nm can deliver DOX to solid tumors to induce significant tumor cell apoptosis and immunogenic cell death (ICD). With the demonstrated intrinsic activity of M‐G1‐TBPNa that can promote the proliferation of natural killer (NK) cells, the ICD‐resulted maturation of dendritic cells of the DOX‐loaded micelles, and the combination of anti‐PD‐L1 antibody, the synergistic modulation of multiple immune cells through NK cell proliferation, recruitment of tumor‐infiltrating NK cells and cytotoxic T cells, and decrease of regulatory T cells for effective tumor chemoimmunotherapy with strong antitumor immunity and immune memory effect for effective prevention of lung metastasis are demonstrated. The developed phosphorous dendron micelles may hold great promise to be used as an advanced nanomedicine formulation for synergistic modulation of multiple immune cells through NK cell proliferation for effective chemoimmunotherapy of different tumor types.
For efficient cancer theranostics, surface modification of nanomaterials plays an important role in improving targeting ability and reducing the non‐specific interactions with normal tissues. Recently, the biomimetic technology represented by coating of cancer cell membranes (CCMs) has been regarded as a promising method to strengthen the biocompatibility and targeting specificity of nanomaterials. Furthermore, the engineered CCMs (ECCMs) integrated with the natural biological properties of CCMs and specific functions from other cells or proteins have offered more possibilities in the field of cancer theranostics. Herein, the recent progresses in the design and preparation of ECCMs are summarized, and the applications of ECCMs in targeting delivery, activation of immunity, and detection of circulating tumor cells are reviewed. Finally, the current challenges and future perspectives with regard to the development of ECCMs are briefly discussed.
Design of intelligent hybrid nanoparticles that can integrate diagnosis and therapy components plays an important role in the field of nanomedicine. Poly(amidoamine) (PAMAM) dendrimers possessing a unique architecture and tunable functional groups have been widely developed for various biomedical applications. Carbon dots (CDs) are considered as a promising fluorescence probe or drug delivery system due to their stable fluorescence property and excellent biocompatibility. The distinctive merits of PAMAM dendrimers and CDs are amenable for them to be constructed as perfect nanohybrids for different biomedical applications, in particular for cancer nanomedicine. Here, the recent advances in the construction of PAMAM dendrimer/CD nanohybrids for diverse biomedical applications, in particular for sensing and cancer theranostics are summarized. Finally, the future perspectives of the PAMAM dendrimer/CD nanohybrids are also briefly discussed.
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