Although
anti-PD-1 immunotherapy is widely used to treat melanoma,
its efficacy still has to be improved. In this work, we present a
therapeutic method that combines immunotherapy and starvation therapy
to achieve better antitumor efficacy. We designed the CMSN-GOx method,
in which mesoporous silica nanoparticles (MSN) are loaded with glucose
oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes
to realize starvation therapy. By functionalizing the MSN’s
biomimetic surfaces, we can synthesize nanoparticles that can escape
the host immune system and homologous target. These attributes enable
the nanoparticles to have improved cancer targeting ability and enrichment
in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors
and induce dendritic cell maturity to stimulate an antitumor immune
response. We performed an in vivo analysis of these
nanoparticles and determined that our combined therapy CMSN-GOx plus
PD-1 exhibits a better antitumor therapeutic effect than therapies
using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission
tomography imaging to measuring the level of glucose metabolism in
tumor tissues, for which we investigate the effect with the cancer
therapy in vivo.
Cell membrane coating nanotechnology, which endows nanoparticles with unique properties, displays excellent translational potential in cancer diagnosis and therapy. However, the preparation and evaluation of these cell membrane-coated nanoparticles are based on cell lines and cell-line-based xenograft mouse models. The feasibility of cell membrane-camouflaged nanomaterials is tested in a preclinical setting.
Head and neck squamous cell carcinoma (HNSCC) patient-derived tumor cell (PDTC) membranes are coated onto gelatin nanoparticles (GNPs) and the resulting PDTC@GNPs show efficient targeting to homotypic tumor cells and tissues in patientderived xenograft (PDX) models. When the donor-derived cell membrane of PDTC@GNPs matched those of the host cells, significant targeting capability is observed. In contrast, mismatch between the donor and host results in weak targeting. Furthermore, it is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin(Pt)-loaded PDTC@GNPs, respectively, lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model. The work presented here reinforces the translation of these biomimetic nanoparticles for clinical applications and offers a simple, safe, and effective strategy for personalized cancer treatment.
Zika virus (ZIKV) has emerged as
a global health threat due to
its unexpected causal link to devastating neurological disorders such
as fetal microcephaly; however, to date, no approved vaccine or specific
treatment is available for ZIKV infection. Here we develop a biomimetic
nanodecoy (ND) that can trap ZIKV, divert ZIKV away from its intended
targets, and inhibit ZIKV infection. The ND, which is composed of
a gelatin nanoparticle core camouflaged by mosquito medium host cell
membranes, effectively adsorbs ZIKV and inhibits ZIKV replication
in ZIKV-susceptible cells. Using a mouse model, we demonstrate that
NDs significantly attenuate the ZIKV-induced inflammatory responses
and degenerative changes and thus improve the survival rate of ZIKV-challenged
mice. Moreover, by trapping ZIKV, NDs successfully prevent ZIKV from
passing through physiologic barriers into the fetal brain and thereby
mitigate ZIKV-induced fetal microcephaly in pregnant mice. We anticipate
that this study will provide new insights into the development of
safe and effective protection against ZIKV and various other viruses
that threaten public health.
It
is well known that the calcium ion is essential for maintaining
life activities in living organisms, and it is of great significance
to detect the intracellular calcium concentration. For the detection
of calcium ions, we developed a new type of fluorescent carbon dots
(CDs), whose surface was modified by ethylenebis(oxyethylenenitrilo)tetraacetic
acid (EGTA) through a secondary hydrothermal method. This is a simple
and convenient chemical preparation method because all reactions are
carried out in the same autoclave, and the final product is directly
the EGTA-modified CDs. The CDs exhibit bright blue fluorescence, and
as the calcium concentration increases, the fluorescence intensity
drops sharply. The fluorescence quenching correlates with the concentration
of calcium ions and has a good linearity in the range of 15–300
μM with a detection limit of 0.38 μM. The experimental
results confirmed that the detection of calcium ions by CDs is a static
fluorescence quenching process. Also, cytotoxicity test and cellular
imaging experiments have shown that the CDs are nontoxic and biocompatible.
Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting. Additionally, they should be harmless and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (FeO NPs). Inherited from the FeO core and the macrophage membrane shell, the resulting FeO@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting and light-to-heat conversion capabilities. Due to the favorable in vitro and in vivo properties, biomimetic FeO@MM NPs were further used for highly effective photothermal therapy of breast cancer in nude mice. Surface modification of synthetic nanomaterials with biomimetic cell membranes exemplifies a novel strategy for designing an ideal nanoplatform for translational medicine.
Recently, RBC membrane coated nanoparticles have attracted much attention because of their excellent immune escape ability; meanwhile, Au nanocages (AuNs) have been extensively used for cancer therapy due to its photothermal effect and drug delivery capability. The combination of RBC membrane coating and Au nanocages may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we present the development of Erythrocyte membrane-coated Gold nanocages for targeted cancer photothermal and chemical therapy. First, anti-EpCam antibodies are used to modify RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel is encapsulated into AuNs. Then, the AuNs are coated with the modified RBC membranes. This new nanoparticles are termed EpCam-RPAuNs. We characterize the capability of EpCam-RPAuNs for selective tumor targeting via exposure to the near-infrared irradiation. Experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validate the biocompatibility of our EpCam-RPAuNs in vitro. By combining the targeting moleculars modified RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.
The polymeric nanogels were constructed via host-guest interactions for dual pH-triggered multistage drug delivery, which showed tumor acidity-triggered nanogel reorganization into smaller nanoparticles for deep tissue penetration, high-efficiency cellular uptake, and intracellular endo-lysosomal pH-responsive drug release.
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