Dendritic Poly Research Articles

Dendritic Polymer-Based Nanomedicines Remodel the Tumor Stroma: Improve Drug Penetration and Enhance Antitumor Immune Response.

The dense extracellular matrix (ECM)insolidtumors, contributed by cancer-associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy of remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote penetration of an immunogenic cell death (ICD) inducer (epirubicin, Epi) via apoptotic vesicles, ultimately enhancing the treatment efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-based nanomedicines (poly[OEGMA-Dendron(G2)-Gly-Phe-Leu-Gly-DAS] (P-DAS) and poly[OEGMA-Dendron(G2)-hydrazone-Epi] (P-Epi)) are developed for sequential delivery of DAS and Epi, respectively. P-DAS reprograms CAFs to reduce collagen by downregulating collagen anabolism and energy metabolism, thereby reducing the ECM deposition. The regulated ECM can enhance tumor penetration of P-Epi to strengthen its ICD effect, leading to an amplified antitumor immune response. In breast cancer-bearing mice, this approach alleviates the ECM barrier, resulting in reduced tumor burden and increased cytotoxic T lymphocyte infiltration, and more encouragingly, synergizes effectively with anti-programmed cell death 1 (PD-1) therapy, significantly inhibiting tumor growth and preventing lung metastasis. Furthermore, systemic toxicity is barely detectable after sequential treatment with P-DAS and P-Epi. This approach opens a new avenue for treating desmoplastic tumors by metabolically targeting CAFs to overcome the ECM barrier.

A co-carrier for plasmid DNA and curcumin delivery to treat pancreatic cancer via dendritic poly(l-lysine) modified amylose

Pancreatic cancer is one of the most lethal malignancies in the world and remains one of the leading causes of cancer related death. For its treatment, a lot of investigations have dealt not only with individual chemotherapy by using polymeric carriers to deliver anticancer drugs, but also with individual gene therapy by using polymeric carriers to deliver nucleic acids such as small interfering RNA (siRNA) and plasmid DNA. However, relatively few studies have been focused on the co-delivery of gene and anticancer drug by multifunctional polymeric carriers for its synergistic therapy. In this work, a DPLL-functionalized amylose (ADP) was prepared by the click reaction between azidized amylose and propargyl focal point poly(l-lysine) dendrons, and then used to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for pancreatic cancer treatment. Due to the internal hydrophobic cavity of amylose component, ADP could load efficiently curcumin with anticancer activity and showed a sustained release behavior. Moreover, the curcumin-loaded ADP could form colloidally stable nanocomplexes with plasmid DNA in aqueous system due to the existence of cationic poly(l-lysine) dendrons and exhibited high gene transfection efficiency. The in vitro and in vivo tests confirmed the effectiveness of using ADP to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for synergistic therapy of pancreatic cancer.

Anticancer Potential of Dendritic Poly(aryl ether)-Substituted Polypyridyl Ligand-Based Ruthenium(II) Coordination Entities.

This paper studies the anticancer potency of dendritic poly(aryl ether)-substituted polypyridyl ligand-based ruthenium(II) coordination entities. The dendritic coordination entities were successfully designed, synthesized, and characterized by different spectral methods such as Fourier transform infrared (FTIR), 1H and 13C- NMR, and mass spectrometry. Further, to understand the structure and solvation behavior of the coordination entities, we performed all-atom molecular dynamics (MD) simulations. The behavior, configuration, and size of the coordination entities in DMSO and water were studied by calculating the radius of gyration (Rg) and solvent-accessible surface area (SASA). The MTT assay was used to assess the in vitro cytotoxicity of all of the coordination entities against cancerous A549 (lung cancer cells), MDA MB 231 (breast cancer cells), and HepG2 (liver cancer cells) and was found to be good with comparable IC50 values with respect to the standard drug cisplatin. The coordination entities exhibited dose dependence, and the highest activity was shown against HepG2 cell lines in comparison to the other cancer cell lines. In addition, fluorescence staining studies, such as AO/EB, DAPI, and cell death analysis by PI staining, were performed on the coordination entities to understand the apoptosis mechanism. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays confirmed apoptosis in cancer cells via the mitochondrial pathway. The DNA fragmentation assay was done followed by molecular docking analysis with DNA executed to strengthen and support the experimental observations.

Comparative Study of the U(VI) Adsorption by Hybrid Silica-Hyperbranched Poly(ethylene imine) Nanoparticles and Xerogels.

Two different silica conformations (xerogels and nanoparticles), both formed by the mediation of dendritic poly (ethylene imine), were tested at low pHs for problematic uranyl cation sorption. The effect of crucial factors, i.e., temperature, electrostatic forces, adsorbent composition, accessibility of the pollutant to the dendritic cavities, and MW of the organic matrix, was investigated to determine the optimum formulation for water purification under these conditions. This was attained with the aid of UV-visible and FTIR spectroscopy, dynamic light scattering (DLS), ζ-potential, liquid nitrogen (LN2) porosimetry, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Results highlighted that both adsorbents have extraordinary sorption capacities. Xerogels are cost-effective since they approximate the performance of nanoparticles with much less organic content. Both adsorbents could be used in the form of dispersions. The xerogels, though, are more practicable materials since they may penetrate the pores of a metal or ceramic solid substrate in the form of a precursor gel-forming solution, producing composite purification devices.

Anti-inflammatory IL-8 Regulation via an Advanced Drug Delivery System at the Oral Mucosa.

Oral inflammatory diseases are highly prevalent in the worldwide population. Topical treatment of inflammation is challenging due to dilution effects of saliva and crevicular fluid. Thus, there is a great medical need to develop smart anti-inflammatory drug delivery systems for mucosa treatment. We compared two promising anti-inflammatory dendritic poly(glycerol-caprolactone) sulfate (dPGS-PCL) polymers for their applicability to the oral mucosa. Using an ex vivo porcine tissue model, cell monolayers, and full-thickness 3D oral mucosal organoids, the polymers were evaluated for muco-adhesion, penetration, and anti-inflammatory properties. The biodegradable dPGS-PCL97 polymers adhered to and penetrated the masticatory mucosa within seconds. No effects on metabolic activity and cell proliferation were found. dPGS-PCL97 revealed a significant downregulation of pro-inflammatory cytokines with a clear preference for IL-8 in cell monolayers and mucosal organoids. Thus, dPGS-PCL97 exhibits excellent properties for topical anti-inflammatory therapy, suggesting new therapeutic avenues in the treatment of oral inflammatory diseases.

Biomimetic dendritic polymeric microspheres induce enhanced T cell activation and expansion for adoptive tumor immunotherapy

A variety of bioactive materials are currently developed to expand T cells ex vivo for adoptive T cell immunotherapy, also known as called artificial antigen-presenting cells (aAPCs). However, almost all the reported designs exhibit relatively smooth surface modified with T cell activating biomolecules, and therefore cannot well mimic the dendritic morphological characteristics of dendritic cells (DCs), the most important type of natural antigen-presenting cells (APCs) with high specific surface areas. Here, we propose a hydrophilic monomer-mediated surface morphology control strategy to synthesize biocompatible dendritic poly(N-isopropylacrylamide) (PNIPAM) microspheres for constructing aAPCs with surface morphology mimicking natural APCs (e.g., DCs). Interestingly, when maintaining the same ligands density, dendritic polymeric microspheres-based aAPCs (DPM beads) can more efficiently expand CD8+ T cells than that with smooth surfaces. Moreover, adoptive transfer of antigen-specific CD8+ T cells expanded by the DPM beads show significant antitumor effect of B16-OVA tumor bearing mice. Therefore, we provide a new concept for constructing biomimetic aAPCs with enhanced T cell expansion ability.

Click Reaction in the Synthesis of Dendrimer Drug-delivery Systems.

Drug delivery systems are designed for the targeted delivery and controlled release of medicinal agents. Among the materials employed as drug delivery systems, dendrimers have gained increasing interest in recent years because of their properties and structural characteristics. The use of dendrimer-nanocarrier formulations enhances the safety and bioavailability, increases the solubility in water, improves stability and pharmacokinetic profile, and enables efficient delivery of the target drug to a specific site. However, the synthesis of dendritic architectures through convergent or divergent methods has drawbacks and limitations that disrupt aspects related to design and construction, and consequently, slow down the transfer from academia to industry. In that sense, the implementation of click chemistry has received increasing attention in the last years, as it offers new efficient approaches to obtain dendritic species in good yields and higher monodispersity. This review focuses on recent strategies for building dendrimer drug delivery systems using click reactions from 2015 to early 2021. The dendritic structures showed in this review are based on β -cyclodextrins (β-CD), poly(amidoamine) (PAMAM), dendritic poly (lysine) (PLLD), dimethylolpropionic acid (bis-MPA), phosphoramidate (PAD), and poly(propargyl alcohol-4-mercaptobutyric (PPMA).

Tumor-acidity and bioorthogonal chemistry-mediated construction and deconstruction of drug depots for ferroptosis under normoxia and hypoxia

Mounting evidence shows that tumor hypoxia stress promotes tumor invasion and metastasis and induces therapeutic resistance. Oxygen-independent Fenton reaction, which refers to the iron-catalyzed conversion of endogenous hydrogen peroxide (H2O2) to hydroxyl radical (·OH), has been designed for ferroptosis therapy. Nevertheless, the treatment efficiency is compromised by limited H2O2 content and limited tumor retention and penetration of nanoparticles. Herein, we designed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots for tumor ferroptosis under normoxia and hypoxia. Briefly, the dendritic poly(amidoamine) (PAMAM, G4) was modified using cinnamaldehyde (CA) to deplete GSH and increase H2O2 levels, and ferrocene (Ferr) served as Fenton reaction catalyst to generate PFC. Subsequently, PFC was modified with maleic acid amide with slow pH-response rate and poly(2-azepane ethyl methacrylate) (PAEMA) with rapid pH-response rate, accompanied with highly efficient bioorthogonal chemistry to construct and deconstruct drug depots for enhanced tumor retention and penetration. The small-sized PFC potentially induced H2O2 self-supplied ferroptosis under normoxia and hypoxia. In sum, this work utilizes two tumoral acidity-responsive groups with different response rates and highly efficient bioorthogonal click chemistry, which paves a way for ferroptosis and provides a general drug delivery strategy with enhanced tumor retention and penetration. Statement of significanceOxygen independent Fenton reaction refers to the conversion of endogenous H2O2 to ·OH which has been designed for ferroptosis therapy. Nevertheless, limited H2O2 level and abundant GSH in tumor cells could both compromise the treatment efficiency. Herein, we developed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots, which elevate the intracellular H2O2 level and deplete GSH for tumor ferroptosis under normoxia and hypoxia microenvironment. This work utilizes two tumoral acidity response groups with different response rates and highly efficient bioorthogonal click reactions, which paves a way for tumor cell ferroptosis and provides a general drug delivery strategy for enhanced tumor accumulation and penetration.

In vitro cytotoxic data on Se-methylselenocysteine conjugated to dendritic poly(glycerol) against human squamous carcinoma cells

Polymeric nanoparticles acting as sources of selenium (Se) are currently an interesting topic in cancer chemotherapy. In this study, polyglycerol dendrimer (DPGLy) was functionalized with seleno-methyl-selenocysteine (SeMeCys) by means of Steglich esterification with 4-dimethylaminopyridine/(l-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (EDC/DMAP) and cerium chloride as cocatalyst in acetonitrile at quantitative yields of 98 ± 1%. The SeMeCys coupling DPGLy efficiency vs. time were determined by Fourier Transform infrared spectroscopy (FTIR) and ultraviolet–visible (UV–Vis) spectroscopy. The cytotoxic effects of SeMeCys–DPGLy on the Chinese Hamster ovary cell line (CHO-K1) and head and neck squamous cell carcinoma (HNSCC) cells line were assessed by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. No signs of general toxicity of SeMeCys–DPGLy against CHO-K1 cells were detectable at which cell viability was greater than 98%. MTS assays revealed that SeMeCys–DPGLy reduced HNSCC cell viability and proliferation at higher doses and long incubation times.

Modification of carbon nanotube with poly(amidoamine) dendritic structures to prepare a multifunctional hybrid curing component for epoxidized polyurethane and novolac resins

Dendritic poly(amidoamine) (PAMAM)-grafted carbon nanotube (CNTD), as a multifunctional hybrid curing component of epoxy-based resins, was prepared using a divergent method. Amino-functionalized CNT was utilized as a core for grafting the first generation of PAMAM dendritic structure by sequential addition of methyl acrylate and ethylenediamine. Epoxy-terminated polyurethane (EPU) and epoxidized novolac resin (ENR) were prepared and used as the epoxy-based polymers of the hybrid composite products. Proton nuclear magnetic resonance spectroscopy was used to study the structure of EPU. Fourier transform infrared spectra were used to prove each of the modification steps during preparation of CNTD. The characteristic peaks of CNTD at 1532 cm−1 originating from combination of stretching and bending vibrations of C–N and N–H bands, respectively, and the peaks at 2930 and 2859 cm−1 assigned to the stretching vibrations of C-H band of methylene groups confirms this claim. In addition, different char residues of CNT and CNTD in thermogravimetric analysis (TGA) curves confirmed addition of the organic parts and successful preparation of CNTD. Structural properties of the hybrid composites were investigated by X-ray diffraction analysis. The hard and soft segment contents of 34.46 and 65.54 wt% were obtained from X-ray diffraction curves. Char contents of 89.6 and 85.6% at 700 °C for the CNT and CNTD shows that the PAMAM modifier content is about 4 wt%. TGA thermograms of the hybrid composites revealed that thermal characteristics of the hybrid composite composed of ENR matrix and high content of CNTD are higher than the other hybrid composites. The ENR-based hybrid composite with 4 wt% of CNTD showed the highest char residue of 55.2% and degradation peak point of 413.6 °C. Morphology of the neat and PAMAM-modified nanotubes were also studied by scanning electron microscopy and transmission electron microscopy.

Development of novel nanocomposite polyurethane ultrafiltration membranes based on multiwalled carbon nanotubes functionalized with PAMAM dendrimer

ABSTRACT Novel biodegradable nanocomposite membranes were prepared using a chemo-enzymatic route. Polyester-urethane-urea matrix was obtained from poly(ε-caprolactone) diol, isophorone diisocyanate (IPDI), and hexamethylene diamine (HMDA) as a chain extender. Nanocomposites (0.5% wt/wt) were synthesized by in situ polymerization using reinforced multi-walled carbon nanotubes (MWNTs) grafted with two distinct-generation dendritic poly(amidoamine) (PAMAM). Membranes were prepared by the so-called inversion phase method, using N,N dimethylformamide as solvent and water as non-solvent. The effect of the amine group content into filler in the mechanical and filtration properties of membranes was evaluated. It was observed that the content of amine groups in the dendrimer-modified MWNTs provides sites for hydrogen bonding interactions in the matrix, which influence mechanical properties such as toughness and extensibility, and the porous morphology of the membrane. Additionally, it was observed that PAMAM grafted MWNTs may interact with soft segments of PU, modifying the filtering properties of membranes.

Convergent click synthesis of macromolecular dendritic β-cyclodextrin derivatives as non-conventional drug carriers: Albendazole as guest model

From a materials science perspective, herein we present the design and synthesis of six macromolecular carbohydrate derivatives, obtained by combining the native cyclic oligosaccharide βCD and dendritic poly(ester) moieties, coupled by CuAAc click reactions, in a convergent fashion. We envisioned two structural variables to promote the formation of inclusion complexes (ICs) with the anti-parasitic drug Albendazole, the degree of substitution on the βCD (mono or hepta-substitution) and the dendritic generation (from first to third). In terms of synthetic effort and cost, the mono-substituted βCD derivatives were obtained in more approachable experimental conditions in comparison to the βCD dendrimers (hepta-substituted macrocycle). The six dendritic derivatives were more soluble in water and showed better complexation capacity than native βCD. For both, mono and hepta-substituted βCD, we observed that the amount of encapsulated ABZ increases when the dendron generation increases. Interestingly, different degrees of substitution (mono and hepta) lead comparable results of ABZ complexation. In conclusion, the encapsulation performance and the consequent solubility enhancement, make these molecular containers excellent materials to positively impact the therapeutic desirability of ABZ.

Dendritic poly(silylene arylacetylene) resins based on 1,3,5-triethynylbenzene

Dendritic poly(silylene arylacetylene) resins based on 1,3,5-triethynylbenzene were synthesized through Grignard reaction. The influences of the content of 1,3,5-triethynylbenzene on the properties of the resin including processability, mechanical properties, heat resistance and thermal stability are studied. Results show that dendritic poly(silylene arylacetylene) resins possess good processability and high mechanical properties while maintaining excellent heat-resistance and thermal stability. The viscosity of dendritic poly(silylene arylacetylene) resins at 90 °C are below 200 mPa·s, and the flexural modulus of the cured DPSA-43H resin is up to 12.65 GPa. The degradation temperatures at 5% weight loss and the residue yield at 800 °C of the cured resins in nitrogen are all above 700 °C and 93%, respectively.

Poly (propylene imine) dendrimer: A potential nanomaterial for electrochemical application

Poly (propylene imine) (PPI) dendrimer has recently received remarkable attention due to its large surface area together with the numerous functional groups present in its end, which helps in binding biological materials or molecules. PPI dendrimers are regarded as nanoscopic architecture and a synthetic macromolecule with highly branched molecular structure with a discrete number of functional end-groups. Interestingly, these functional groups play significant roles in the immobilisation of biological molecules. Poly (propylene mine) (PPI) dendrimer acts as nanomediator and has been reportedly used for the fabrication of numerous electrochemical biosensors and sensors for various applications. Electrochemical techniques such as impedimetric, electrochemiluminescence, potentiometric and amperometric are employed for the quantification of target biomolecules, with high selectivity and sensitivity. Dendritic poly (propylene imine) has been reportedly employed in the construction of immunosensors, DNA biosensors, enzyme biosensors and chemical sensors. Despite extensive research and numerous reports, the PPI dendrimer-based sensor and biosensor application has rarely been reported. Therefore, this review covers the panoramic accounts on the applications of PPI for the fabrication of electrochemical biosensors and sensors. This review highlights the important applications of PPI dendrimer in the field of electrochemical biosensors and sensors.

Nonionic Amphiphilic Linear Dendritic Block Copolymers. Solvent-Induced Self-Assembly and Morphology Tuning

In this article, we report the solution self-assembly of a series of amphiphilic linear–dendritic block copolymers (LDBCs), which are composed of hydrophilic dendritic poly(ether-ester), PEE, blocks based on 2,2-bis(hydroxymethyl)propionic acid and hydrophobic linear poly(styrene), PSt, blocks. The investigated LDBCs have narrow dispersity with three PEE generations (1–3) and a broad range of PSt molecular masses and are produced by dendron-initiated atom transfer radical polymerization of styrene followed by deprotection of the peripheral dendron hydroxyl groups. The solution self-assembly of the copolymers is performed by slowly adding water to the polymer solution in tetrahydrofuran (THF) as the common solvent for both blocks of the copolymers. The morphologies of the supramolecular assemblies are preserved either by diluting their dispersion by excess of water or by THF evaporation. It is found that the micellar morphology (sphere, wormlike, and/or vesicle) depends on the hydrophilic block fraction (F...

Immunomodulatory Effects of Dendritic Poly(ethyleneimine) Glycoarchitectures on Human Multiple Myeloma Cell Lines, Mesenchymal Stromal Cells, and in Vitro Differentiated Macrophages for an Ideal Drug Delivery System in the Local Treatment of Multiple Myeloma.

The use of a drug delivery system (DDS) represents a novel therapeutic approach in the treatment of multiple myeloma in bone lesion. We show the immunomodulatory effects of anionic and cationic dendritic poly(ethyleneimine) glycoarchitectures (PEI-DGAs) on human myeloma cell lines and cells in their microenvironment, in vitro differentiated macrophages, and mesenchymal stromal cells (MSCs). PEI-DGAs do not influence the secretion of IL-6, which is a major growth and survival factor in multiple myeloma. Cationic PEI-DGAs in turn have cytostatic properties on multiple myeloma cell lines. Anionic PEI-DGAs induce the secretion of proinflammatory cytokines IL-1β, TNFα, and IL-6 in macrophages and MSCs, whereas cationic PEI-DGAs do not. Macrophages and MSCs show remarkably high cell viability in the presence of high concentration of PEI-DGAs. RNA sequencing of MSCs exposed to cationic PEI-DGAs supports the hypothesis that smaller cationic PEI-DGAs are less toxic and could improve osteogenic differentiation in an ideal DDS.

Controlled ATRP Synthesis of Novel Linear-Dendritic Block Copolymers and Their Directed Self-Assembly in Breath Figure Arrays.

Herein, we report the formation and characterization of novel amphiphilic linear-dendritic block copolymers (LDBCs) composed of hydrophilic dendritic poly(ether-ester), PEE, blocks and hydrophobic linear poly(styrene), PSt. The LDBCs are synthesized via controlled atom transfer radical polymerization (ATRP) initiated by a PEE macroinitiator. The copolymers formed have narrow molecular mass distributions and are designated as LGn-PSt Mn, in which LG represents the PEE fragment, n denotes the generation of the dendron (n = 1–3), and Mn refers to the average molecular mass of the LDBC (Mn = 3.5–68 kDa). The obtained LDBCs are utilized to fabricate honeycomb films by a static “breath figure” (BF) technique. The copolymer composition strongly affects the film morphology. LDBCs bearing acetonide dendron end groups produce honeycomb films when the PEE fraction is lower than 20%. Pore uniformity increases as the PEE content decreases. For LDBCs with hydroxyl end groups, only the first generation LDBCs yield BF films, but with a significantly smaller pore size (0.23 μm vs. 1–2 μm, respectively). Although higher generation LDBCs with free hydroxyl end groups fail to generate honeycomb films by themselves, the use of a cosolvent or addition of homo PSt leads to BF films with a controllable pore size (3.7–0.42 μm), depending on the LDBC content. Palladium complexes within the two triazole groups in each of the dendron’s branching moieties can also fine-tune the morphology of the BF films.

π-Stacking Interactions of Graphene-Coated Cobalt Magnetic Nanoparticles with Pyrene-Tagged Dendritic Poly(Vinylidene Fluoride).

This study investigates the non-covalent coating of cobalt magnetic nanoparticles (MNPs) involving a graphene surface with pyrene-tagged dendritic poly(vinylidene fluoride) (PVDF). Dendrimers bearing a pyrene moiety were selected to play the role of spacers between the graphene surface of the MNPs and the PVDF chains, the pyrene unit being expected to interact with the surface of the MNPs. The pyrene-tagged dendritic spacer 11 decorated with ten acetylenic units was prepared and fully characterized. Azido-functionalized PVDF chains were then grafted onto each branch of the dendrimer using Huisgen's [3+2] cycloaddition reaction. Next, the association of the resulting pyrene-tagged dendritic PVDF 13 with commercially available Co/C MNPs by π-stacking interactions was studied by fluorescence spectroscopy. Evaluated were the stability of the π-stacking interactions when the temperature increased and the reversibility of the process when the temperature decreased. Also, hybrid MNPs were prepared from pyrene-tagged dendrimers decorated either with acetylenic functions (11) or with PVDF branches (13), and they were characterized by transmission electron microscopy and comparative elemental analysis was carried out with naked MNPs.

Liposomal formulation of polyacrylate-peptide conjugate as a new vaccine candidate against cervical cancer

Peptide-based vaccines have been proposed as a therapeutic strategy for many infectious diseases, including human papilloma virus (HPV)-related cervical cancer. Peptide-based vaccines are a better treatment option than traditional chemotherapeutic agents and surgery, as they rely on the use of the body’s immune system to fight cancer cells, resulting in minimal risk of side effects. However, to increase the efficacy of peptide-based vaccines, the application of potent adjuvant and a suitable delivery system is essential. In this study, we developed a self-adjuvanting delivery system based on a combination of polymer and liposomes, for a therapeutic vaccine against cervical cancer. Peptide epitope (8Qm) derived from HPV-16 E7 protein was conjugated to dendritic poly(tert-butyl acrylate) as a primary delivery system and incorporated into cationic liposomes, which served as a secondary delivery system. Our vaccine candidate was able to kill established HPV-16 E7-positive tumor (TC-1) cells in mice following a single immunization. The immunized mice had 80% survival rate after two months. In contrast, both polymer-8Qm conjugate and liposomes bearing 8Qm failed to eradicate TC-1 tumors. The survival rate of mice was only 20% when immunized with 8Qm formulated with standard incomplete Freund’s adjuvant.

An Update on Design and Pharmacology of Dendritic Poly(l-lysine)

Dendritic nanomaterials are unique due to their flexible architectures. So far, many structural analogues of dendritic poly(l-lysine) have been developed. Since its monomer unit is a biodegradable amino acid, poly(l-lysine) derived nanocarriers are biocompatible and safe. In this overview, structural diversity of dendritic poly(l-lysine) scaffold and patents filed on them so far are described. Furthermore, biopharmaceutical properties and therapeutic activity modulations observed from their drug delivery applications are highlighted. Poly(l-lysine) based dendriplexes, dendrosomes and dendrisomes remain novel and nearly unexplored. Since structural modifications can control the biopharmaceutical properties of aforementioned scaffold, achieving programmed drug delivery is possible. Many such structures have demonstrated not only excellent carrier characteristics but few intrinsic therapeutic activities also. A poly(l-lysine) dendrimer product VivaGel is currently under consideration in a new drug application category of various regulatory bodies. As dendritic poly(l-lysine) scaffold is biocompatible unlike many other nanocarriers, its clinical utilization would prove considerably beneficial.