Recent advances in multifunctional dendrimer-based complexes for cancer treatment.

The application of nanotechnology in biological and medical fields have resulted in the creation of new devices, supramolecular systems, structures, complexes, and composites. Dendrimers are relatively new nanotechnological polymers with unique features; they are globular in shape, with a topological structure formed by monomeric subunit branches diverging to the sides from the central nucleus. This review analyzes the main features of dendrimers and their applications in biology and medicine regarding cancer treatment. Dendrimers have applications that include drug and gene carriers, antioxidant agents, imaging agents, and adjuvants, but importantly, dendrimers can create complex nanosized constructions that combine features such as drug/gene carriers and imaging agents. Dendrimer-based nanosystems include different metals that enhance oxidative stress, polyethylene glycol to provide biosafety, an imaging agent (a fluorescent, radioactive, magnetic resonance imaging probe), a drug or/and nucleic acid that provides a single or dual action on cells or tissues. One of major benefit of dendrimers is their easy release from the body (in contrast to metal nanoparticles, fullerenes, and carbon nanotubes), allowing the creation of biosafe constructions. Some dendrimers are already clinically approved and are being used as drugs, but many nanocomplexes are currently being studied for clinical practice. In summary, dendrimers are very useful tool in the creation of complex nanoconstructions for personalized nanomedicine. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Brain Delivery of Biomimetic Phosphorus Dendrimer/Antibody Nanocomplexes for Enhanced Glioma Immunotherapy via Immune Modulation of T Cells and Natural Killer Cells.

Fully mobilizing the activities of multiple immune cells is crucial to achieve the desired tumor immunotherapeutic efficacy yet still remains challenging. Herein, we report a nanomedicine formulation based on phosphorus dendrimer (termed AK128)/programmed cell death protein 1 antibody (aPD1) nanocomplexes (NCs) that are camouflaged with M1-type macrophage cell membranes (M1m) for enhanced immunotherapy of orthotopic glioma. The constructed AK128-aPD1@M1m NCs with a mean particle size of 160.3 nm possess good stability and cytocompatibility. By virtue of the decorated M1m having α4 and ß1 integrins, the NCs are able to penetrate the blood-brain barrier to codeliver both AK128 with intrinsic immunomodulatory activity and aPD1 to the orthotopic glioma with prolonged blood circulation time. We show that the phosphorus dendrimer AK128 can boost natural killer (NK) cell proliferation in peripheral blood mononuclear cells, while the delivered aPD1 enables immune checkpoint blockade (ICB) to restore the cytotoxic T cells and NK cells, thus promoting tumor cell apoptosis and simultaneously decreasing the tumor distribution of regulatory T cells vastly for improved glioma immunotherapy. The developed nanomedicine formulation with a simple composition achieves multiple modulations of immune cells by utilizing the immunomodulatory activity of nanocarrier and antibody-mediated ICB therapy, providing an effective strategy for cancer immunotherapy.

Unsymmetrical Low-Generation Cationic Phosphorus Dendrimers as a Nonviral Vector to Deliver MicroRNA for Breast Cancer Therapy.

The development of nonviral dendritic polymers with a simple molecular backbone and great gene delivery efficiency to effectively tackle cancer remains a great challenge. Phosphorus dendrimers or dendrons are promising vectors due to their structural uniformity, rigid molecular backbones, and tunable surface functionalities. Here, we report the development of a new low-generation unsymmetrical cationic phosphorus dendrimer bearing 5 pyrrolidinium groups and one amino group as a nonviral gene delivery vector. The created AB5-type dendrimers with simple molecular backbone can compress microRNA-30d (miR-30d) to form polyplexes with desired hydrodynamic sizes and surface potentials and can effectively transfect miR-30d to cancer cells to suppress the glycolysis-associated SLC2A1 and HK1 expression, thus significantly inhibiting the migration and invasion of a murine breast cancer cell line in vitro and the corresponding subcutaneous tumor mouse model in vivo. Such unsymmetrical low-generation phosphorus dendrimers may be extended to deliver other genetic materials to tackle other diseases.

Bioactive Phosphorus Dendrimers as a Universal Protein Delivery System for Enhanced Anti-inflammation Therapy.

Nanocarrier-based cytoplasmic protein delivery offers opportunities to develop protein therapeutics; however, many delivery systems are positively charged, causing severe toxic effects. For enhanced therapeutics, it is also of great importance to design nanocarriers with intrinsic bioactivity that can be integrated with protein drugs due to the limited bioactivity of proteins alone for disease treatment. We report here a protein delivery system based on anionic phosphite-terminated phosphorus dendrimers with intrinsic anti-inflammatory activity. A phosphorus dendrimer termed AK-137 with optimized anti-inflammatory activity was selected to complex proteins through various physical interactions. Model proteins such as bovine serum albumin, ribonuclease A, ovalbumin, and fibronectin (FN) can be transfected into cells to exert their respective functions, including cancer cell apoptosis, dendritic cell maturation, or macrophage immunomodulation. Particularly, the constructed AK-137@FN nanocomplexes display powerful therapeutic effects in acute lung injury and acute gout arthritis models by integrating the anti-inflammatory activity of both the carrier and protein. The developed anionic phosphite-terminated phosphorus dendrimers may be employed as a universal carrier for protein delivery and particularly utilized to deliver proteins and fight different inflammatory diseases with enhanced therapeutic efficacy.

Phosphorus core-shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters.

Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core-shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with 99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with 99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.

"Click" Chemistry for the Functionalization of Graphene Oxide with Phosphorus Dendrons: Synthesis, Characterization and Preliminary Biological Properties.

Two families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified-GO and GO-dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses. In addition, the free dendrons and the dendrons grafted to GO were tested toward cancerous (HCT116) and non-cancerous (RPE1) cell lines.

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells.

Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation.

Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis.

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain. The dendriplexes demonstrated the ability to protect siRNA from nuclease degradation and to promote macrophage uptake. Moreover, they led to potent inhibition of TNF-α expression in the lipopolysaccharide-activated mouse macrophage cell line RAW264.7 in vitro model. A significant anti-inflammatory effect in the murine collagen-induced arthritis model was observed through arthritis scoring and histological observations. These results open up essential perspectives in using this original amphiphilic dendron to reduce the disease burden and improve outcomes in chronic inflammatory diseases.

Cationic phosphorus dendron nanomicelles deliver microRNA mimics and microRNA inhibitors for enhanced anti-inflammatory therapy of acute lung injury.

The development of efficient nanomedicines to repress the repolarization of M1 phenotype macrophages and therefore inhibit pro-inflammatory cytokine overexpression for anti-inflammatory therapy is still a challenging task. We report here an original gene delivery nanoplatform based on pyrrolidinium-modified amphiphilic generation 1 phosphorus dendron (C12G1) nanomicelles with a rigid phosphorous dendron structure. The nanomicelles display higher gene delivery efficiency than the counterpart materials of pyrrolidinium-modified G1 phosphorus dendrimers, and meanwhile exhibit excellent cytocompatibility. The C12G1 nanomicelles can be employed to co-deliver the miRNA-146a mimic (miR-146a mimic) and miRNA-429 inhibitor (miR-429i) to inhibit the Toll-like receptor-4 signaling pathway and p38 mitogen-activated protein kinase signaling pathway, respectively, thus causing repression of M1 phenotype alveolar macrophage polarization. The developed C12G1/miR-mixture polyplexes enable efficient therapy of lipopolysaccharide-activated alveolar macrophages in vitro and an acute lung injury mouse model in vivo. The generated cationic phosphorus dendron nanomicelles may hold promising potential for anti-inflammatory gene therapy of other inflammatory diseases.

Amphiphilic phosphorous dendron micelles co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy.

Combined chemo/gene therapy of cancer through different action mechanisms has been emerging to enhance the therapeutic efficacy towards cancer, and still remains a challenging task due to the lack of highly effective and biocompatible nanocarriers. In this work, we report a new nanosystem based on amphiphilic phosphorus dendron (1-C12G1) micelles to co-deliver microRNA-21 inhibitor (miR-21i) and doxorubicin (DOX) for combination therapy of triple negative breast cancer. The amphiphilic phosphorus dendron bearing a long linear alkyl chain and ten protonated pyrrolidine surface groups was prepared and was demonstrated to form micelles in water solution and have a hydrodynamic size of 103.2 nm. The micelles are shown to be stable, enable encapsulation of an anticancer drug DOX with optimal loading content (80%) and encapsulation efficiency (98%), and can compress miR-21i to form polyplexes to render it with good stability against degradation. The co-delivery system of 1-C12G1@DOX/miR-21i polyplexes has a pH-dependent DOX release profile, and can be readily phagocytosed by cancer cells to inhibit them due to the different anticancer mechanisms, which was further validated after intravenous injection to treat an orthotopic triple-negative breast tumor model in vivo. With the proven biocompatibility under the studied doses, the developed amphiphilic phosphorus dendron micelles could be developed as an effective nanomedicine formulation for synergistic cancer therapy.

Phosphorous Dendron Micelles as a Nanomedicine Platform for Cooperative Tumor Chemoimmunotherapy via Synergistic Modulation of Immune Cells.

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.

Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise Review.

Curcumin (Cur), a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. However, the poor water solubility and low bioavailability of Cur limit its therapeutic effects for clinical applications. A variety of nanocarriers have been successfully developed to improve the water solubility, in vivo distribution, and pharmacokinetics of Cur, as well as to enhance the ability of Cur to polarize macrophages and relieve macrophage oxidative stress or anti-apoptosis, thus accelerating the therapeutic effects of Cur on inflammatory diseases. Herein, we review the design and development of diverse Cur nanoformulations in recent years and introduce the biomedical applications and potential therapeutic mechanisms of Cur nanoformulations in common inflammatory diseases, such as arthritis, neurodegenerative diseases, respiratory diseases, and ulcerative colitis, by regulating macrophage behaviors. Finally, the perspectives of the design and preparation of future nanocarriers aimed at efficiently exerting the biological activity of Cur are briefly discussed.

Engineered phosphorus dendrimers as powerful non-viral nanoplatforms for gene delivery: a great hope for the future of cancer therapeutics.

During the past two decades, tremendous progress has been made in the dendrimer-based delivery of therapeutic molecules including, for instance, small molecules, macromolecules, and genes. This review deals with recent successes in the development of promising biocompatible phosphorus dendrimers, a specific type of dendrimer, to deliver genes to treat cancers.

Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

Construction of multifunctional nanoplatforms to elevate chemotherapeutic efficacy and induce long-term antitumor immunity still remains to be an extreme challenge. Herein, the design of an advanced redox-responsive nanomedicine formulation based on phosphorus dendrimer-copper(II) complexes (1G3 -Cu)- and toyocamycin (Toy)-loaded polymeric nanoparticles (GCT NPs) coated with cancer cell membranes (CM) are reported. The designed GCT@CM NPs with a size of 210 nm are stable under physiological conditions but are rapidly dissociated in the reductive tumor microenvironment to deplete glutathione and release drugs. The co-loading of 1G3 -Cu and Toy within the NPs causes significant tumor cell apoptosis and immunogenic cell death through 1G3 -Cu-induced mitochondrial dysfunction and Toy-mediated amplification of endoplasmic reticulum stress, respectively, thus effectively suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. Likewise, the coated CM and the loaded 1G3 -Cu render the GCT@CM NPs with homotypic targeting and T1 -weighted magnetic resonance imaging of tumors, respectively. With the assistance of programmed cell death ligand 1 antibody, the GCT@CM NP-mediated chemotherapy can significantly potentiate tumor immunotherapy for effective inhibition of tumor recurrence and metastasis. The developed GCT@CM NPs hold a great potential for chemotherapy-potentiated immunotherapy of different tumor types through different mechanisms or synergies.

Engineered Stable Bioactive Per Se Amphiphilic Phosphorus Dendron Nanomicelles as a Highly Efficient Drug Delivery System To Take Down Breast Cancer In Vivo.

Conventional small molecular chemical drugs always have challenging limitations in cancer therapy due to their high systemic toxicity and low therapeutic efficacy. Nanotechnology has been applied in drug delivery, bringing new promising potential to realize effective cancer treatment. In this context, we develop here a new nanomicellar drug delivery platform generated by amphiphilic phosphorus dendrons (1-C17G3.HCl), which could form micelles for effective encapsulation of a hydrophobic anticancer drug doxorubicin (DOX) with a high drug loading content (42.4%) and encapsulation efficiency (96.7%). Owing to the unique dendritic rigid structure and surface hydrophilic groups, large steady void space of micelles can be created for drug encapsulation. The created DOX-loaded micelles with a mean diameter of 26.3 nm have good colloidal stability. Strikingly, we show that the drug-free micelles possess good intrinsic anticancer activity and act collectively with DOX to take down breast cancer cells in vitro and the xenografted tumor model in vivo through upregulation of Bax, PTEN, and p53 proteins for enhanced cell apoptosis. Meanwhile, the resulting 1-C17G3.HCl@DOX micelles significantly abolish the toxicity relevant to the free drug. The findings of this study demonstrate a unique nanomicelle-based drug delivery system created with the self-assembling amphiphilic phosphorus dendrons that may be adapted for chemotherapy of different cancer types.

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells.

Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development.

Dendrimeric HIV-peptide delivery nanosystem affects lipid membranes structure.

The aim of this study was to evaluate the nature and mechanisms of interaction between HIV peptide/dendrimer complexes (dendriplex) and artificial lipid membranes, such as large unilayered vesicles (LUV) and lipid monolayers in the air-water interface. Dendriplexes were combined as one of three HIV-derived peptides (Gp160, P24 and Nef) and one of two cationic phosphorus dendrimers (CPD-G3 and CPD-G4). LUVs were formed of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) or of a mixture of DMPC and dipalmitoyl-phosphatidylglycerol (DPPG). Interactions between dendriplexes and vesicles were characterized by dynamic light scattering (DLS), fluorescence anisotropy, differential scanning calorimetry (DSC) and Langmuir-Blodgett methods. The morphology of formed systems was examined by transmission electron microscopy (TEM). The results suggest that dendriplexes interact with both hydrophobic and hydrophilic regions of lipid bilayers. The interactions between dendriplexes and negatively charged lipids (DMPC-DPPG) were stronger than those between dendriplexes and liposomes composed of zwitterionic lipids (DMPC). The former were primarily of electrostatic nature due to the positive charge of dendriplexes and the negative charge of the membrane, whereas the latter can be attributed to disturbances in the hydrophobic domain of the membrane. Obtained results provide new information about mechanisms of interaction between lipid membranes and nanocomplexes formed with HIV-derived peptides and phosphorus dendrimers. These data could be important for the choosing the appropriate antigen delivery vehicle in the new vaccines against HIV infection.

First-in-Class Phosphorus Dendritic Framework, a Wide Surface Functional Group Palette Bringing Noteworthy Anti-Cancer and Anti-Tuberculosis Activities: What Lessons to Learn?

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.

Engineered non-invasive functionalized dendrimer/dendron-entrapped/complexed gold nanoparticles as a novel class of theranostic (radio)pharmaceuticals in cancer therapy.

Nanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia, a large variety of dendrimers, i.e. soft artificial macromolecules, have turned up as non-viral functional nanocarriers for entrapping drugs, imaging agents, and targeting molecules. This review will provide insights into the design, synthesis, functionalization, and development in biomedicine of engineered functionalized hybrid dendrimer-tangled gold nanoparticles in the domain of cancer theranostic. Several aspects are highlighted and discussed such as 1) dendrimer-entrapped gold(0) hybrid nanoparticles for the targeted imaging and treatment of cancer cells, 2) dendrimer encapsulating gold(0) nanoparticles (Au DENPs) for the delivery of genes, 3) Au DENPs for drug delivery applications, 4) dendrimer encapsulating gold radioactive nanoparticles for radiotherapy, and 5) dendrimer/dendron-complexed gold(III) nanoparticles as technologies to take down cancer cells.

Facile Synthesis of Amphiphilic Fluorescent Phosphorus Dendron-Based Micelles as Antiproliferative Agents: First Investigations.

We designed and synthesized several families of novel amphiphilic fluorescent phosphorus dendron-based micelles showing relevant antiproliferative activities for use in the field of theranostic nanomedicine. Based on straightforward synthesis pathways, 12 amphiphilic phosphorus dendrons bearing 10 protonated cyclic amino groups (generation one), or 20 protonated amino groups (generation two), and 1 hydrophobic chain carrying 1 fluorophore moiety were created. The amphiphilic dendron micelles had the capacity to aggregate in solution using hydrophilic/hydrophobic interactions, which promoted the formation of polymeric micelles. These dendron-based micelles showed moderate to high antiproliferative activities against a panel of tumor cell lines. This paper presents for the first time the synthesis and our first investigations of new phosphorus dendron-based micelles for cancer therapy applications.