Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis

Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs. 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs. 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

Photodynamic therapy (PDT) is a promising anticancer noninvasive method and has great potential for clinical applications. Unfortunately, PDT still has many limitations, such as metastatic tumor at unknown sites, inadequate light delivery and a lack of sufficient oxygen. Recent studies have demonstrated that photodynamic therapy in combination with other therapies can enhance anticancer effects. The development of new nanomaterials provides a platform for the codelivery of two or more therapeutic drugs, which is a promising cancer treatment method. The use of multifunctional nanocarriers for the codelivery of two or more drugs can improve physical and chemical properties, increase tumor site aggregation, and enhance the antitumor effect through synergistic actions, which is worthy of further study. This review focuses on the latest research progress on the synergistic enhancement of PDT by simultaneous multidrug administration using codelivery nanocarriers. We introduce the design of codelivery nanocarriers and discuss the mechanism of PDT combined with other antitumor methods. The combination of PDT and chemotherapy, gene therapy, immunotherapy, photothermal therapy, hyperthermia, radiotherapy, sonodynamic therapy and even multidrug therapy are discussed to provide a comprehensive understanding.

Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.

PhotothermalPhage: A Virus-Based Photothermal Therapeutic Agent

ABSTRACT: Virus-like particles (VLPs) are multifunctional nanocarriers that mimic the architecture of viruses. They can serve as a safe platform for specific functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, a new generation immunophotothermal agent is developed that adjuvants photothermal ablation using a chemically modified VLP called bacteriophage Qβ. The design is based on the conjugation of near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turns it to a powerful NIR-absorber called Photothermal Phage. This system can generate more heat upon 808 nm NIR laser radiation than free dye and possesses a photothermal efficiency comparable to gold nanostructures, yet it is biodegradable and acts as an immunoadjuvant combined with the heat it produces. The synergistic combination of thermal ablation with the mild immunogenicity of the VLP leads to effective suppression of primary tumors, reduced lung metastasis, and increased survival time.

Dual-ligated Metal Organic Framework as Novel Multifunctional Nanovehicle for Targeted Drug Delivery for Hepatic Cancer Treatment

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.

Bioengineered Ferritin Nanocarriers for Cancer Therapy

Ferritin naturally exists in most organisms and can specifically recognize the transferrin 1 receptor (TfR1), which is generally highly expressed on various types of tumor cells. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. Recent studies, further establish ferritin as a multifunctional nanocarrier for targeted cancer chemotherapy and phototherapy. In this review, we introduce the favorable characteristics of ferritin drug carriers, the specific targeted surface modification and a multifunctional nanocarriers combined chemotherapy with phototherapy for tumor treatment. Taken together, ferritin is a potential ideal base of engineered nanoparticles for tumor therapy and still needs to explore more on its way.

PhotoPhage: A Virus-based Photothermal Therapeutic Agent

ABSTRACT: Virus like particles (VLPs) are non-infectious multifunctional nanocarriers with the pathogenic-like architecture of viruses. They can serve as a safe platform for precise functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, we describe the development of novel immunophotothermal agent for combinatorial photothermal ablation and immunotherapy based on VLP of bacteriophage Qβ. The design was based on covalent conjugation of 212 water soluble near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turned it to a powerful NIR-absorber with photothermal efficiencies exceeding that of gold nanostructures. This PhotoPhage system generates heat upon 808 nm NIR laser radiation and causes significant cellular cytotoxicity that prevents the progression of primary tumors in mice. It is found that PhotoPhage not only acts as a PTT agent that initiates anti-tumor immune response, but also simultaneously acts as an immunoadjuvant that promotes maturation of dendritic cells, triggers T lymphocyte cells (CD4+, CD8+) and reduces suppressive T regulatory cells leading to effective suppression of primary tumors, reducing lung metastases, and increasing survival time.

PhotoPhage: A Virus-based Photothermal Therapeutic Agent

ABSTRACT: Virus like particles (VLPs) are non-infectious multifunctional nanocarriers with the pathogenic-like architecture of viruses. They can serve as a safe platform for precise functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, we describe the development of novel immunophotothermal agent for combinatorial photothermal ablation and immunotherapy based on VLP of bacteriophage Qβ. The design was based on covalent conjugation of 212 water soluble near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turned it to a powerful NIR-absorber with photothermal efficiencies exceeding that of gold nanostructures. This PhotoPhage system generates heat upon 808 nm NIR laser radiation and causes significant cellular cytotoxicity that prevents the progression of primary tumors in mice. It is found that PhotoPhage not only acts as a PTT agent that initiates anti-tumor immune response, but also simultaneously acts as an immunoadjuvant that promotes maturation of dendritic cells, triggers T lymphocyte cells (CD4+, CD8+) and reduces suppressive T regulatory cells leading to effective suppression of primary tumors, reducing lung metastases, and increasing survival time.