Human epidermal growth factor receptor 2 (HER2) is overexpressed in over 20% of breast cancers. The dimerization of HER2 receptors leads to the activation of downstream signals enabling proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2-positive breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles in aqueous conditions, but, upon binding to HER2 on cancer cells, transform into nanofibers, which Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Size-transformable nanomedicine has the potential to overcome systemic and local barriers, leading to efficient accumulation and penetration throughout the tumor tissue. However, the design of this type of nanomedicine was seldom based on active targeting and intracellular size transformation. Here, we report an intracellular size-transformable nanosystem, in which small and positively charged nanoparticles (<30 nm) prepared from the self-assembly of an amphiphilic hexadecapeptide derivative was coated by folic acid- and dopamine-decorated hyaluronan (HA) to form large and negatively charged nanoparticles (∼130 nm). This nanosystem has been proven to improve the blood circulation half-life of the drug and prevent premature intravascular drug leakage from the nanocarrier. Once accumulated in the tumor, the nanoparticles were prone to HA- and folic acid-mediated cellular uptake, followed by intracellular size transformation and discharge of transformed small nanoparticles. The size-transformable nanosystem facilitated the transcytosis-mediated tumor penetration and improved the internalization of nanoparticles by cells and the intracellular release of 7-ethyl-10 hydroxycamptothecin. With an indocyanine green derivative as the intrinsic component of the amphiphilic polymer, the nanosystem has exhibited additional theranostic functions: photoacoustic imaging, NIR-laser-induced drug release, and synergistic chemotherapy and phototherapy, leading to a 50% complete cure rate in a subcutaneous B16 melanoma model. This nanosystem with multimodalities and efficient tumor penetration has shown potentials in improving anticancer efficacy.
for various fields, such as drug delivery, [1,2] biosensing, [3] detoxification, [4] and environmental remediation. [5] These miniaturized machines can convert local fuel or external energy (e.g., magnetic, ultrasound, or light) to driving force and obtain selfpropulsion in dynamic surroundings. [6] Due to the increasing demands and rigorous requirements of biomedical community, the composition of microrobots has been evolving from rigid and inorganic materials to functional and endogenous cells. [7] Incorporating natural cells with synthetic micromachines creates an elegant platform with synergistic properties of cell biofunctionalities and effective propulsion. The cargo-loading capability of cells is employed by cell-based microrobots to actively deliver drugs, [2,[8][9][10][11] such as red blood cell (RBC)based micromotors loaded with doxorubicin (DOX) and photosensitizer, [10,11] and neutrophil-based microrobots carrying paclitaxel (PTX). [2] However, the utilized chemotherapeutic agents in the robotic system are not specific to cancerous cells and occur drug leakage during transport, inducing unavoidable toxicity to normal regions along with limited therapeutic efficacy and undesired side effects. [12] Such compromised biosafety and antitumor index hinder the practical A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe 3 O 4 nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.
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