Cellular Delivery Systems Research Articles

HGG-49. INTERNEURONS THAT BITE: A CELLULAR DELIVERY SYSTEM FOR PEDIATRIC HIGH-GRADE GLIOMA

Abstract BACKGROUND High-grade gliomas (HGG) represent the leading cause of cancer-related mortality in children due to a lack of curative therapies. Challenges of cellular therapies in brain tumors include the lack of unique tumor antigens, downregulation of targeted antigens, and immune suppressive tumor microenvironment. To circumvent these obstacles, we devised a cellular delivery system using post-mitotic migratory cortical inhibitory interneuron precursors (MCIPs) to deliver therapeutic payloads in an antigen-independent manner. Notably, HGGs secrete the same chemoattractants stimulating long-distance MCIP migration as during normal fetal development, leading to the hypothesis that MCIPs would preferentially migrate to HGG cells. METHODS MCIP to HGG cell migration was assessed in vitro using transwell migration assays, and in vivo via stereotactic injection of MCIP and glioma xenografts in nude mice. As proof of principle, MCIPs were equipped with an EGFR or CD19 control bispecific T-cell engager (BiTE) which activates T-cells upon their linkage to the tumor cells resulting in glioma elimination. Equipped MCIPs were co-cultured with HGG cells and CD8 T-cells at an effector to target ratio of 4:1. Results were validated in vivo via xenografts of HGG, MCIPs, and either a single dose of CD8 T-cells or repeated T-cell dosing via intraventricular cannula. Survival was evaluated via Kaplan-Meier curves. RESULTS MCIPs migrated preferentially to the majority of HGG cell lines in vitro and in vivo. This migration was mediated, at least in part, via CXCR4 ligands. MCIPs secreting an EGFR-BiTE potently killed HGG cells in vitro versus CD19-BiTE controls. Furthermore, nude mice xenografted with HGG and EGFR-expressing MCIPs experienced prolonged survival versus controls. CONCLUSION These data suggest that MCIPs form a viable cellular delivery system and can be equipped with various agents targeting HGG. Modified MCIPs could be differentiated from induced pluripotent stem cells and injected into the resection cavity margins to eliminate residual cells.

EXTH-29. INTERNEURONS THAT BITE, A CELLULAR THERAPY FOR HIGH GRADE GLIOMA

Abstract Glioblastoma has a poor prognosis with limited therapeutic options. Cellular therapies, like CAR-T therapy, have unfortunately shown limited efficacy for brain tumors, due to the lack of unique tumor antigens, the downregulation of targeted antigens, and the immune suppressive tumor microenvironment (TME). To circumvent these brain tumor specific obstacles, we developed a cellular immunotherapy delivery system, derived from post-mitotic Migratory Cortical Inhibitory Interneuron Precursors (MCIPs), that induces a cytotoxic tumor response in glioblastoma independent of unique tumor antigens. During fetal brain development, MCIPs are chemoattracted to migrate long distances from their subcortical origins into the cerebral cortex. The MCIP chemoattractant CXCL12 activates CXCR4 to induce this migration. Intriguingly, CXCL12 is secreted by glioblastoma, suggesting they chemoattract MCIPs. Excitingly, our in vitro and in vivo data indeed show that MCIPs robustly migrate to the majority of glioblastoma cell lines evaluated. Crucially, this migration is independent of unique tumor antigens and the TME and provides us with the opportunity to use MCIPs as a delivery vector for cytotoxic agents. In one approach, we successfully eliminated EGFR expressing glioblastoma in vivo by modifying MCIPs to secrete EGFR Bispecific T-cell Engagers (BiTE). BiTE engagement with a tumor cell results in T-cell activation and elimination of the engaged tumor cell. Importantly, the T-cells have no innate recognition of the tumor cell, this is provided by the BiTE. Local EGFR BiTE secretion has limited systemic toxicity, thereby making EGFR a viable non-unique target. MCIPs can be equipped with a range of agents that eliminate glioblastoma. As a therapy, we envisage injecting modified MCIPs, differentiated from patient or donor “off the shelf” induced pluripotent stem cells, into the margin of the surgical cavity to “clean-up” tumor cells remaining post-surgery. An interneuron clinical trial for epilepsy (NCT05135091) is ongoing, highlighting the translational potential of our MCIP cellular therapy.

Recent Advancement in Ocular Drug Delivery System: A Systematic Review

Recent scientific and technological advancements have made ophthalmology a top priority for the study of therapeutic products, including the creation, preclinical testing, and clinical evaluation of novel medications, medical devices, and drug-medical device combinations. In order to decrease metabolism and elimination and increase residence time in ocular tissues and compartments, sustained-release drug delivery systems such as liposomes, micelles, nano-emulsions, nanoparticles with colloidal structures, and intraocular implants have been developed. Research is also being conducted in the area of cutting-edge medicines, including those based on gene or cell systems, both of which are considered high-risk products because to their intricate structures. Regarding the definition of drug (medicinal product) and recent changes in regulation, this article reviews recent advancements in ophthalmic drug, gene, and cellular delivery systems and related goods as well as breakthroughs in advanced therapeutic medicinal Products.

Systemic Tumor Suppression via Macrophage-Driven Automated Homing of Metal-Phenolic-Gated Nanosponges for Metastatic Melanoma.

Cell-based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug-loading with high accumulations in solid tumors. Herein, a tumor-targeting cellular drug delivery system (MAGN) by surface engineering of tumor-homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron-tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the "ON-OFF" gating effect of the polyphenol-based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor-targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs.

Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Loss of multipotency in adipose-derived stem cells after culture in temperature-responsive injectable polymer hydrogels

Adipose-derived stem cells (AdSCs), a type of mesenchymal stem cell, are expected to be applicable to regenerative medicine and cellular delivery systems. The maintenance of cell multipotency and control of the differentiation direction are important for these applications. However, the differentiation direction of these cells is widely believed to depend on the physical properties of their scaffold. In this study, we explored whether the multipotency of AdSCs, that is, their ability to differentiate into multiple cells, is maintained when they are removed from injectable polymer (IP) hydrogels with various degrees of cross-linking and induced to differentiate into osteoblasts and adipocytes. We confirmed that AdSCs cultured in IP hydrogels maintained an undifferentiated state. However, their differentiation into osteoblasts and adipocytes cannot be ensured; specifically, the multipotency of AdSCs may decrease when they are cultured in IP hydrogels. When cultured in an IP hydrogel with extreme softness and poor cell adhesion properties, the AdSCs remained in an undifferentiated state, but their multipotency was reduced. These results provide important insights into stem cell delivery systems using IP hydrogels.

Preparation and characterization of gadolinium-based thermosensitive liposomes: A potential nanosystem for selective drug delivery to cancer cells

Gadodiamide (Gd-DTPA-BMA) is a gadolinium-based complex, used as a contrast agent in magnetic resonance imaging procedures. Recent studies revealed the capacity of this complex of inducing apoptosis in neoplastic cells. However, a great challenge for its use as an anticancer drug is low cellular internalization and drug delivery systems such as thermosensitive liposomes can be a strategy to overcome these limitations and increase anti-tumor efficacy. In this context, this study aimed to develop, characterize, and assess the cytotoxic activity and selectivity index of thermosensitive liposomes containing Gd-DTPA-BMA. Formulations were prepared by the lipid film hydration method and their physicochemical, morphological, and thermal properties were evaluated. Cell viability was performed 4T1/MDA-MB-231 tumor cells and WI-26 VA4 normal cells. Transmission electron microscopy analyses showed high electron density in the inner core of Gd-DTPA-BMA-loaded liposomes that can be attributed to the Gd-DTPA-BMA, since Gd-loaded nanosystems present low light transmittance and high electron density by this technique. The dynamic light scattering, differential scanning calorimetry, small-angle X-ray scattering, and in vitro release results confirm that the lipid composition was suitable since Tc (temperature of the transition Lβ → Lα) values are in accordance with those reported for thermosensitive liposomes used in the treatment of cancer. The cytotoxic studies against breast cancer cell lines demonstrated that the Gd-DTPA-BMA-loaded liposomes have higher cytotoxicity than free Gd-DTPA-BMA. Moreover, these liposomes presented minimal toxicity in a normal cell line when compared to the free Gd-DTPA-BMA. Therefore, the results of this study suggest that thermosensitive liposomes containing Gd-DTPA-BMA might be a new promising nanocarrier system for breast cancer treatment.

Multifunctional injectable pluronic-cystamine-alginate-based hydrogel as a novel cellular delivery system towards tissue regeneration

This paper presents a new thermal sensitive hydrogel system based on cystamine-functionalised sodium alginate-g-pluronic F127 (ACP). The introduction of cystamine to the alginate backbone not only creates a covalent bond with pluronic F127 but also provides intrinsic anti-bacterial activity for the resultant hydrogel. The amount of water uptake inside the hydrogel remained ~200% for 6 days and the degradation was completed in 12 days in physiological media. The ACP copolymer solution could form a hydrogel at body temperature (~37 °C) and could return to the solution phase if the temperature decreased below 25o °C. Fibroblast encapsulated in situ in the ACP hydrogel maintained their viability (≥90% based on the live/dead assay) for 7 days, demonstrating the good biocompatibility of the ACP hydrogel for long-term cell cultivation. In addition, three-dimensional (3D) culture showed that fibroblast attached to the hydrogels and successfully mimicked the porous structure of the ACP hydrogel after 5 days of culture. Fibroblast cells could migrate from the cell-ACP clusters and form a confluent cell layer on the surface of the culture dish. Altogether, the obtained results indicate that the thermal-responsive ACP hydrogel synthesised in this study may serve as a cellular delivery platform for diverse tissue engineering applications.

Pluronic F-127/Silk Fibroin for Enhanced Mechanical Property and Sustained Release Drug for Tissue Engineering Biomaterial.

Herein, an injectable thermosensitive hydrogel was developed for a drug and cellular delivery system. The composite was prepared by facile physical mixing of pluronic F-127 (PF) and silk fibroin (SF) in an aqueous solution. The chemical structure, transparency, viscosity, injectability, degradation kinetic, cumulative release of dexamethasone (Dex), a type of corticosteroid drug, and size distribution of the fabricated hydrogels were characterized. Cytotoxicity of the hydrogels was also studied to verify the biocompatibility of the hydrogels. The addition of a proper amount of SF to PF not only improved the mechanical strength but also decreased the degradation rate which improved the fast rate release of hydrophobic drugs. The cytotoxicity of the hydrogel decreased when SF was added to PF in a proper amount. Overall, the results confirm that the composite of PF and SF can be a promising cell and drug delivery system for future application in tissue engineering and regenerative medicine.

Frontiers in the treatment of glioblastoma: Past, present and emerging.

Glioblastoma (GBM) is one of the most aggressive cancers of the brain. Despite extensive research over the last several decades, the survival rates for GBM have not improved and prognosis remains poor. To date, only a few therapies are approved for the treatment of GBM with the main reasons being: 1) significant tumour heterogeneity which promotes the selection of resistant subpopulations 2) GBM induced immunosuppression and 3) fortified location of the tumour in the brain which hinders the delivery of therapeutics. Existing therapies for GBM such as radiotherapy, surgery and chemotherapy have been unable to reach the clinical efficacy necessary to prolong patient survival more than a few months. This comprehensive review evaluates the current and emerging therapies including those in clinical trials that may potentially improve both targeted delivery of therapeutics directly to the tumour site and the development of agents that may specifically target GBM. Particular focus has also been given to emerging delivery technologies such as focused ultrasound, cellular delivery systems nanomedicines and immunotherapy. Finally, we discuss the importance of developing novel materials for improved delivery efficacy of nanoparticles and therapeutics to reduce the suffering of GBM patients.

Erythrocyte as novel cellular drug delivery system

Nowadays so many carrier systems are used for delivery of drug or any other therapeutic agent to specific tissues or cells for achieving desired therapeutic efficacy. Using drug delivery systems can improve action of therapeutic agent and reduce their toxicity. As a novel approach the erythrocyte or red blood cells are used for drug delivery. The resealed erythrocyte is a cellular carrier have more advantage than other carrier system. Based on various studies found that erythrocyte have greater potential in delivery of biopharmaceuticals, therapeutically significant peptides and proteins, nucleic acid-based biological, antigens, anticancer drug and vaccines. The main problem obtain in case of existing carrier systems are biocompatibility of carrier and its degradation products. The biocompatibility, non-pathogenicity, non-immunogenicity and biodegradability make erythrocyte unique and useful carriers. They also possess longer circulation half-life and zero order drug release kinetics. Resealed erythrocyte carriers have certain impact among the activity of certain therapeutic agent like anti-inflammatory drugs, steroids, chemotherapeutic agents by reducing their side effect upon incorporation with these carriers. The general preparation step of resealed erythrocyte involve separation of erythrocyte from blood the organism of interest and using different methods the erythrocyte broken and the therapeutic agent or drug entrapped into the erythrocyte. This review article highlights the characteristics, isolation techniques of erythrocyte, preparation method, evaluation, application of resealed erythrocyte as carrier in drug delivery systems.

Influence of Size and Cross-Linking Density of Microgels on Cellular Uptake and Uptake Kinetics

The unique pH and temperature responsiveness of PNIPAM-based microgels make them a promising target for novel biomedical applications such as cellular drug delivery systems. However, we lack a comprehensive understanding of how the physicochemical properties of microgels relate to their interaction with cells. Here, we show that HEK293T cells take up PNIPAM-based microgels on a second-to-minute time scale. Uptake rates are determined by microgel size and cross-linker content. Using fluorescence confocal live-cell microscopy, we observe microgel uptake in real time and describe cellular uptake kinetics. Experiments reveal that small and less cross-linked microgels show faster uptake kinetics than microgels of larger size or higher cross-linker content. Only microgels that are larger than 800 nm in diameter and have cross-linking contents of 10-15 mol % do not show translocation into cells. Together, these results provide insight into microgel-cell interactions and generate quantitative information on the deterministic role of microgel architecture-i.e., size and rigidity-for uptake by a prototypical human cell line.

Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.

Ocular Drug, Gene and Cellular Delivery Systems and Advanced Therapy Medicinal Products.

Due to recent advances in science and technology, when the products used in therapy are examined, ophthalmology has a priority in terms of research and development, preclinical and clinical studies of innovative drugs, medical devices and drug-medical device combination products. Liposomes, micelles, nanoemulsions, nanoparticles with colloidal structures and intraocular implants as sustained-release drug delivery systems have been developed to overcome the barriers to ocular applications, increase absorption, decrease metabolism and elimination and increase the residence time in ocular tissues and compartments. Studies are also ongoing in the area of advanced therapies using gene or cell-based systems which are high-risk products due to their complex structures. In this review, ocular drug, gene and cellular delivery systems and related products and developments in advanced therapy medicinal products are presented in respect to the definition of drug (medicinal product) and current changes in legislation.

Camptothecin-loaded fusogenic nanodroplets as ultrasound theranostic agent in stem cell-mediated drug-delivery system

Adipose-derived stem cells (ADSCs) have been utilized in cellular delivery systems to carry therapeutic agents into tumors by migration. Drug-loaded nanodroplets release drugs and form bubbles after acoustic droplet vaporization (ADV) triggered by ultrasound stimulation, providing a system for ultrasound-induced cellular delivery of theranostic agents. In order to improve the efficiency of drug release, fusogenic nanodroplets were designed to go from nano to micron size upon uptake by ADSCs for reducing ADV threshold. The purpose of our study was to demonstrate the utility of camptothecin-loaded fusogenic nanodroplets (CPT-FNDs) as ultrasound theranostic agents in an ADSCs delivery system. CPT-FNDs showed an increase in size from 81.6 ± 3.5 to 1043.5 ± 28.3 nm and improved CPT release from 22.0 ± 1.8% to 37.6 ± 2.1%, demonstrating the fusion ability of CPT-FNDs. CPT-FNDs-loaded ADSCs demonstrated a cell viability of 77 ± 4%, and the in vitro migration ability was 3.2 ± 1.2-fold for the tumor condition compared to the cell growth condition. Ultrasound enhancement imaging showed intratumoral ADV-generated bubble formation (increasing 3.24 ± 0.47 dB) triggered by ultrasound after CPT-FNDs-loaded ADSCs migration into B16F0 tumors. Histological images revealed intratumoral distribution of CPT-FNDs-loaded ADSCs and tissue damage due to the ADV. The CPT-FNDs can be used as theranostic agents in an ADSCs delivery system to provide the ultrasound contrast imaging and deliver combination therapy of drug release and physical damage after ADV.

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems.

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal “virtual laboratory” for such multicellular systems simulates both the biochemical microenvironment (the “stage”) and many mechanically and biochemically interacting cells (the “players” upon the stage). PhysiCell—physics-based multicellular simulator—is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility “out of the box.” The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a “cellular cargo delivery” system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant independent code base for replicating results from other simulation platforms. The PhysiCell source code, examples, documentation, and support are available under the BSD license at http://PhysiCell.MathCancer.org and http://PhysiCell.sf.net.

DNA tetrahedron nanostructures for biological applications: biosensors and drug delivery.

With the rapid development of DNA nanotechnology, various DNA nanostructures with different shapes and sizes have been self-assembled using "bottom-up" fabrication strategies and applied to a wide range of fields such as biosensors, drug delivery and tools for molecular biology. As a classical and simple polyhedron, DNA tetrahedron can be easily synthesised by a one-step assembly. Due to the excellent biocompatibility and cellular permeability, it provides a universal and promising platform to construct a series of biosensors and drug delivery systems for living cells studies. Moreover, the high programmability of DNA tetrahedron determines its capability to perform artful design and combine with other materials. Herein, we review and summarise the development and applications of DNA tetrahedron in living cell studies. We mainly focus on two parts, cellular biosensors for the detection of nucleic acids, proteins, small molecules and cancer cells and drug delivery systems for chemotherapy, immunotherapy, photodynamic therapy and gene silencing. With the rapid progress in DNA tetrahedron as well as DNA nanotechnology, new avenues and opportunities have opened up in analytical chemistry, molecular biology and medicine.

Synthesis and optimization of a reactive oxygen species responsive cellular delivery system

Reactive oxygen species responsive delivery systems for the detection of peroxides in live macrophages have been designed. The oxidative cleavage of a boronic ester to a phenol triggered by hydrogen peroxide followed by self-immolation of a ROS-sensitive cleavable linkervia1,6-elimination allowed the disturbance of the fluorescence resonance energy transfer turning on the near-infrared fluorescence.

Peripheral Nerve Regeneration Through Hydrogel-Enriched Chitosan Conduits Containing Engineered Schwann Cells for Drug Delivery.

Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-2(18kDa)) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-2(18kDa) overexpressing SCs.

Intracellular cargo delivery by virus capsid protein-based vehicles: From nano to micro

Cellular delivery is an important concern for the efficiency of medicines and sensors for disease diagnoses and therapy. However, this task is quite challenging. Self-assembly virus capsid proteins might be developed as building blocks for multifunctional cellular delivery vehicles. In this work, we found that SV40 VP1 (Simian virus 40 major capsid protein) could function as a new cell-penetrating protein. The VP1 protein could carry foreign proteins into cells in a pentameric structure. A double color structure, with red QDs (Quantum dots) encapsulated by viral capsids fused with EGFP, was created for imaging cargo delivery and release from viral capsids. The viral capsids encapsulating QDs were further used for cellular delivery of micron-sized iron oxide particles (MPIOs). MPIOs were efficiently delivered into live cells and controlled by a magnetic field. Therefore, our study built virus-based cellular delivery systems for different sizes of cargos: protein molecules, nanoparticles, and micron-sized particles. From the Clinical EditorMuch research is being done to investigate methods for efficient and specific cellular delivery of drugs, proteins or genetic material. In this article, the authors describe their approach in using self-assembly virus capsid proteins SV40 VP1 (Simian virus 40 major capsid protein). The cell-penetrating behavior provided excellent cellular delivery and should give a new method for biomedical applications.