Mediated Cancer Therapy Research Articles

Multi‐Enzyme Mimetic MoCu Dual‐Atom Nanozyme Triggering Oxidative Stress Cascade Amplification for High‐Efficiency Synergistic Cancer Therapy

AbstractSingle‐atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)‐mediated cancer therapy. However, the high energy barriers of reaction intermediates on single‐atom sites and the overexpressed antioxidants in the tumor microenvironment restrict the amplification of tumor oxidative stress, resulting in unsatisfactory therapeutic efficacy. Herein, we report a multi‐enzyme mimetic MoCu dual‐atom nanozyme (MoCu DAzyme) with various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared with Mo SAzyme, the introduction of Cu atoms, formation of dual‐atom sites, and synergetic catalytic effects among various active sites enhance substrate adsorption and reduce the energy barrier, thereby endowing MoCu DAzyme with stronger catalytic activities. Benefiting from the above enzyme‐like activities, MoCu DAzyme can not only generate multiple ROS, but also deplete GSH and block its regeneration to trigger the cascade amplification of oxidative stress. Additionally, the strong optical absorption in the near‐infrared II bio‐window endows MoCu DAzyme with remarkable photothermal conversion performance. Consequently, MoCu DAzyme achieves high‐efficiency synergistic cancer treatment incorporating collaborative catalytic therapy and photothermal therapy. This work will advance the therapeutic applications of DAzymes and provide valuable insights for nanocatalytic cancer therapy.

Conformational Switch of a Peptide Provides a Novel Strategy to Design Peptide Loaded Porous Organic Polymer for Pyroptosis Pathway Mediated Cancer Therapy.

While peptide-based drug development is extensively explored, this strategy has limitations due to rapid excretion from the body (or shorter half-life in the body) and vulnerability to protease-mediated degradation. To overcome these limitations, a novel strategy for the development of a peptide-based anticancer agent is introduced, utilizing the conformation switch property of a chameleon sequence stretch (PEP1) derived from a mycobacterium secretory protein, MPT63. The selected peptide is then loaded into a new porous organic polymer (PG-DFC-POP) synthesized using phloroglucinol and a cresol derivative via a condensation reaction to deliver the peptide selectively to cancer cells. Utilizing ensemble and single-molecule approaches, this peptide undergoes a transition from a disordered to an alpha-helical conformation, triggered by the acidic environment within cancer cells that is demonstrated. This adopted alpha-helical conformation resulted in the formation of proteolysis-resistant oligomers, which showed efficient membrane pore-forming activity selectively for negatively charged phospholipids accumulated in cancer cell membranes. The experimental results demonstrated that the peptide-loaded PG-DFC-POP-PEP1 exhibited significant cytotoxicity in cancer cells, leading to cell death through the Pyroptosis pathway, which is established by monitoring numerous associated events starting from lysosome membrane damage to GSDMD-induced cell membrane demolition. This novel conformational switch-based drug design strategy is believed to have great potential in endogenous environment-responsive cancer therapy and the development of future drug candidates to mitigate cancers.

Bacterial immunotherapy: is it a weapon in our arsenal in the fight against cancer?

Advances in understanding the genetic basis of cancer have driven alternative treatment approaches. Recent findings have demonstrated the potential of bacteria and it's components to serve as robust theranostic agents for cancer eradication. Compared to traditional cancer therapies like surgery, chemotherapy, radiotherapy, bacteria mediated tumor therapy has exhibited superior cancer suppressing property which is attributed a lot to it's tumor proliferating and accumulating characteristics. Genetically modified bacteria hasreduced inherent toxicity and enhanced specificity towards tumor microenvironment. This anti- tumor activity of bacteria is attributed to its toxins and other active components from the cell membrane, cell wall and spores. Furthermore, bacterial genes can be regulated to express and deliver cytokines, antibodies and cancer therapeutics. Although there is less clinical data available, the pre- clinical research clearly indicates the feasibility and potential of bacteria- mediated cancer therapy.

Discovery of novel organoarsenicals as robust thioredoxin reductase inhibitors for oxidative stress mediated cancer therapy

Targeting overexpressed thioredoxin reductase (TrxR) in cancer cells to induce oxidative stress has been proved to be an effective strategy for cancer therapy. However, the treatment was hindered by the low efficiency and frequent administration of TrxR inhibitors, and hence more potent TrxR inhibitors were urgently needed. Herein, we designed and synthesized a series of TrxR inhibitors based on arsenicals. Among these, compound 1d inhibited the proliferation of a variety of cancer cells at low micromolar concentrations and exhibited low toxicity to normal cells. Importantly, compound 1d induced the accumulation of reactive oxygen species (ROS) by inhibiting the TrxR activity, further causing the collapse of the redox system, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and DNA damage, followed by oxidative stress-induced cell apoptosis. In vivo data showed that, compared with the clinical TrxR inhibitor auranofin (AUR), compound 1d could more effectively eliminate tumors by 90 % at a dose of 1.5 mg/kg without any obvious side effects. These results indicated that compound 1d was a potent TrxR inhibitor against cancer.

Recent Advances in Polyoxometalate Based Nanoplatforms Mediated Reactive Oxygen Species Cancer Therapy.

The potential of reactive oxygen species (ROS) cancer therapy in tumor treatment has been greatly enhanced by the introduction of catalytically superior polyoxometalate (POM)-based nanoplatforms, mainly composed of atomic clusters consisting of pre-transition metals and oxygen. These nanoplatforms have unique advantages, such as Fenton activity at neutral pH, induction of cellular ferroptosis instead of just apoptosis, and sensitivity to external field stimulation. However, there are also inevitable challenges such as neutralization of ROS by the antioxidant system of the tumor microenvironment (TME), hypoxia, and limited hydrogen peroxide concentrations. This review article aims to provide an overview of recent research advancements in POM-based nanoplatforms for ROS therapy from the perspective of chemical reactions and biological processes, addressing endogenous and exogenous factors that affect the antitumor efficacy. Endogenous factors include the mechanism of ROS generation by POM, the impact of pH and antioxidant systems on POM, and the various manners of tumor cell death. Exogenous stimuli mainly include light, heat, X-rays, and electricity. The article analyzes the specific mechanisms of action of each influencing factor in the first two sections, concluding with the limitations of the present study and some possible directions for future research.

Thermal damage analysis of sub-surface soft tissue sarcoma for indocyanine green mediated photothermal cancer therapy

Photothermal therapy is a minimal invasive technique to treat tumors situated near the skin or other light accessible organs. Here, a photothermal agent is delivered to tumor either intratumorally or intravenously and the tumor is irradiated with near infrared (NIR) radiation to generate heat for thermal damage of tumor. In this paper, thermal damage of soft tissue sarcoma, a type of sub-surface forearm tumor, is evaluated for photothermal therapy using numerical simulations. Indocyanine green (ICG) is used as photothermal agent and the effect of various spatial distributions and doses of ICG for sub surface tumors located at various depths (3–6 mm) were investigated. Further, numerical simulation is validated experimentally through tumor-tissue mimicking phantoms. Computations were performed in MATLAB software using Lattice Boltzmann method and validated through experiments using tumor-tissue mimicking phantoms. Results show that the thermal damage region (damage parameter (Ω) of magnitude 4.6) was enlarged on increasing the concentration of ICG while it got shrunk for the deeper tumors. Computations reveal that ICG concentration of 50 μg/mL is optimum, for intravenous distribution, for photothermal therapy with minimal damage to surrounding tissue. It is found that irradiation duration of more than 900 s is required to achieve the complete damage of tumor. For the case of deeper tumors, about 1200 s of exposure is required, at irradiation intensity of 0.25 W/cm2. This study provides a numerical approach to determine therapeutic parameters and demonstrates the thermal damage for subsurface tumors through ICG mediated photothermal therapy by proper selection of therapeutic parameters.

Cu2+-Pyropheophorbide a-Cystine Conjugate: Synergistic Photodynamic/Chemodynamic Therapy and Glutathione Depletion Improves the Antitumor Efficacy and Downregulates the Hypoxia-Inducing Factor.

Cancer immune escape, metastasis, recurrence, and multidrug resistance are all associated with hypoxia in the tumor microenvironment (TME). We synthesized a CuPPaCC conjugate for reactive oxygen species (ROS)-mediated cancer therapy. CuPPaCC continuously produced cytotoxic ROS and oxygen through a photo-chemocycloreaction, alleviated hypoxia, and inhibited the expression of a hypoxia-inducing factor (HIF-1α). CuPPaCC was synthesized from pyromania phyllophyllic acid a (PPa), cystine (CC), and copper ions, and its structure was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The ability of CuPPaCC to produce ROS and oxygen after photodynamic therapy (PDT) in vitro and in vivo was investigated. The ability of CuPPaCC to consume glutathione was investigated. CuPPaCC toxicity (light and dark) in CT26 cells was analyzed by MTT and live/dead cell staining. The anticancer effect of CuPPaCC in vivo was investigated in CT26 Balb/c mice. When stimulated by the TME, CuPPaCC released Cu2+ and PPaCC, and the singlet oxygen yield increased from 34 to 56.5%. The dual ROS-generating mechanism via a Fenton-like reaction/photoreaction and dual glutathione depletion via Cu2+/CC multiplied the antitumor efficacy of CuPPaCC. The photo-chemocycloreaction continued to produce oxygen and maintained high ROS levels even after PDT, significantly alleviating hypoxia in the TME and downregulating the expression of HIF-1α. CuPPaCC thus showed excellent antitumor activity in vitro and in vivo. These results showed that the strategy could be effective in improving the antitumor efficacy of CuPPaCC and could be used as a synergistic regimen for cancer therapy.

Biomineralized CO gas-releasing nanoprodrug for endoplasmic reticulum stress mediated cancer therapy

Biomineralized CO gas-releasing nanoprodrug for endoplasmic reticulum stress mediated cancer therapy

An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy.

Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are the most clinically advanced but they require cumbersome four components and suffer from inflammation-related side effects that should be minimized for safety. Yet, a certain level of proinflammatory responses and innate immune activation are required to evoke T-cell immunity for mRNA cancer vaccination. To address these issues and develop potent yet low-inflammatory mRNA cancer vaccine vectors, a series of alternating copolymers "PHTA" featured with ortho-hydroxy tertiary amine (HTA) repeating units for mRNA delivery is synthesized, which can play triple roles of condensing mRNA, enhancing the polymeric nanoparticle (PNP) stability, and prolonging circulation time. Unlike LNPs exhibiting high levels of inflammation, the PHTA-based PNPs show negligible inflammatory side effects in vivo. Importantly, the top candidate PHTA-C18 enables successful mRNA cancer vaccine delivery in vivo and leadsto a robust CD8+ T cell mediated antitumor cellular immunity. Such PHTA-based integrated PNP provides a potential approach for establishing mRNA cancer vaccines with good inflammatory safety profiles.

A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients’ quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

HXV2O5 Nanocatalysts Combined with Ultrasound for Triple Amplification of Oxidative Stress to Enhance Cancer Catalytic Therapy

AbstractMultiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)‐mediated cancer therapy. Herein, vanadium‐based nanocatalysts, hydrogen vanadium bronzes (HXV2O5, for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi‐functional catalytic activity in decomposing H2O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS‐mediated cancer therapies.

HX V2 O5 Nanocatalysts Combined with Ultrasound for Triple Amplification of Oxidative Stress to Enhance Cancer Catalytic Therapy.

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.

Tumor Microenvironment-Responsive Cu/CaCO3 -Based Nanoregulator for Mitochondrial Homeostasis Disruption-Enhanced Chemodynamic/Sonodynamic Therapy.

The efficiency of reactive oxygen species (ROS)-mediated cancer therapy is restrained by intrinsic characteristics in the tumor microenvironment (TME), such as overexpressed glutathione (GSH), hypoxia and limited efficiency of H2 O2 . In this work, intelligent copper-dropped calcium carbonate loading sonosensitizer Ce6 nanoparticles (Cu/CaCO3 @Ce6, CCC NPs) are established to realize TME-responsive self-supply of oxygen and successively Ca2+ -overloading-strengthened chemodynamic therapy/sonodynamic therapy (CDT/SDT). CCC NPs release Ca2+ , Cu2+ , and Ce6 in weakly acid and GSH-excessive TME. Released Cu2+ can not only consume GSH and turn into Cu+ via a redox reaction, but also provide CDT-creating hydroxyl radicals through the Fenton-like reaction. Under ultrasound irradiation, the intracellular oxidative stress is amplified profoundly relying on singlet oxygen outburst from SDT. Moreover, Ca2+ influx aggravates the mitochondrial disruption, which further accelerates the oxidation level. The facile and feasible design of the Cu-dropped CaCO3 -based nanoregulators will be further developed as a paradigm in ROS-contributed cancer therapy.

Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy.

Despite all sorts of innovations in medical researches over the past decades, cancer remains a major threat to human health. Mitochondria are essential organelles in eukaryotic cells, and their dysfunctions contribute to numerous diseases including cancers. Mitochondria-targeted cancer therapy, which specifically delivers drugs into the mitochondria, is a promising strategy for enhancing anticancer treatment efficiency. However, owing to their special double-layered membrane system and highly negative potentials, mitochondria remain a challenging target for therapeutic agents to reach and access. Polymeric nanoparticles exceed in cancer therapy ascribed to their unique features including ideal biocompatibility, readily design and synthesis, as well as flexible ligand decoration. Significant efforts have been put forward to develop mitochondria-targeted polymeric nanoparticles. In this review, we focused on the smart design of polymeric nanosystems for mitochondria targeting and summarized the current applications in improving cancer therapy.

Salmonella Typhimurium as a potential anticancer agent: A Review

Bacteria mediated cancer therapy has not been used as much as other methods, despite being considered a potential adjunct in anticancer therapeutic strategy for decades. However, in recent years, there has been considerable interest in exploration of the option of bacteria mediated cancer immunotherapy. The conventional anticancer therapy does not eradicate cancer completely. It often fails and has several other limitations which can easily be overcome through the bacteria mediated approach as an adjunctive therapy. Members of the genus Salmonella have the ability to colonize all forms of tumours and their metastasis much more efficiently than other bacteria. Salmonella has over 2500 serovars of which Salmonella Typhimurium, a non-typhoidal strain, is the most extensively studied for its anticancer activity. S. Typhimurium has the intrinsic attribute of being able to selectively colonize solid tumours and their metastasis. S. Typhimurium is able to target and destroy tumours in three specific ways; inducing immune response to the presence of tumours, utilizing bacterial toxins to directly activate caspase-3, ( an important enzyme of the apoptotic pathway) and also as a vector in delivering of anti-cancer compounds to tumour sites. S. Typhimurium is currently considered as a bacterium with great potential in the field of cancer immunotherapy. In this review, the explanation of the mechanisms of anticancer activity of live attenuated and engineered S. Typhimurium strains in vitro and in vivo is attempted.

FGFR1 overexpression renders breast cancer cells resistant to metformin through activation of IRS1/ERK signaling

Metformin has been suggested as an anti-cancer agent. However, increasing reports show that some tumors are resistant to metformin. Identification of factors affecting metformin mediated cancer therapy is of great significance. FGFR1 is a receptor-tyrosine-kinase that is frequently overexpressed in breast cancer, which is associated with poor-prognosis. To investigate the effect of FGFR1 overexpression on metformin-induced inhibition of breast cancer cells, we demonstrated that FGFR1 overexpression rendered MCF-7 and T47D cells resistant to metformin. In particular, we found that, in addition to AKT and ERK1/2 activation, FGFR1-induced activation of IRS1 and IGF1R, key regulators connecting metabolism and cancer, was associated with metformin resistance. Targeting IRS with IRS1 KO or IRS inhibitor NT157 significantly sensitized FGFR1 overexpressing cells to metformin. Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR. Moreover, we demonstrated that IRS1 functions as a critical mediator of the crosstalk between FGFR1 and IGF1R pathways, which involves a feedback loop between IRS1 and MAPK/ERK. Our study highlights the significance of FGFR1 status and IRS1 activation in metformin-resistance, which will facilitate the development of strategies targeting FGFR overexpression-associated metformin resistance.

Liposomal nanotheranostics for multimode targeted in vivo bioimaging and near\u2010infrared light mediated cancer therapy

Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and emissive graphene quantum dots (GQDs) were engineered named as NFGL. Further, doxorubicin hydrochloride was encapsulated in NFGL to exhibit phototriggered chemotherapy and functionalized with folic acid targeting ligands. Encapsulated agents showed imaging bimodality for in vivo tumor diagnosis due to their high contrast and emissive nature. Targeted NFGL nanohybrids demonstrated near infrared light (NIR, 750 nm) mediated tumor reduction because of generated heat and Reactive Oxygen Species (ROS). Moreover, NFGL nanohybrids exhibited remarkable ROS scavenging ability as compared to GQDs loaded liposomes validated by antitumor study. Hence, this approach and engineered system could open new direction for targeted imaging and cancer therapy.

New Approaches for T Cell Immunomodulation

Cancer is one of the leading causes of death worldwide. Despite the evolution in cancer treatment, the mortality rate is still high. The astonishing results of immune checkpoint inhibitors in patients bearing solid tumors have encouraged scientists to develop new strategies for cancer immunotherapy to further improve the clinical outcomes. Immunomodulation for cancer therapy is growing rapidly as a promising alternative approach for conventional cancer therapeutics, due to its specificity and efficacy in suppressing growth and metastasis. However, the complexity of the tumor microenvironment and the various mechanisms whereby tumor cells escape the immune response diminishes the efficacy of many cancer immunotherapeutic drugs, especially when the drug is administered as monotherapy. Some of these factors include poor immune recognition of tumor cells, lack of sufficient drug concentration within the tumor site, and suppression of tumor-reactive T cell proliferation and effector functions. This review describes some of the novel immunomodulation strategies that have been recently developed to overcome these limitations and to augment strong antitumor immune response against different tumor types. For example, monoclonal antibodies (mAbs), CAR- T cells, Bi-specific T-cell engagers (BiTE) antibody, oncolytic viruses (OVs), cytokine-antibody fusion protein, genetically engineered mesenchymal stem cells (MSCs), oncolytic virotherapy, gut microbiota modulation and nanoparticles mediated cancer therapy. These novel strategies have been proven to augment strong antitumor immune response against different tumor types, reduced toxicity, as well as generated long-lived memory T cell population that was able to protect the host from tumor relapse. Combination therapies either with conventional or immunotherapy further improved the efficacy of cancer treatment.

Nanoconfinement-mediated cancer theranostics.

Despite various therapeutic or diagnostic developments, cancer is still one of the most lethal diseases due to insufficiently adequate treatments and the delay of the early stage of disease detection. An image-guided drug delivery system (IGDDS), as a real-time noninvasive imaging assessment of therapeutic response, has the strong potential to improve the diagnosis and treatment of cancer because its imaging property offers the quantification of nanomedicine at the intended disease sites, the possible assurance of adequate treatment and elimination of undesirable delay of early-stage diagnosis due to low resolution. One of potential modality that overcomes these challenges could be the nanoconfinement of gold (Au) nanoparticles within other nanoparticles called "Particle-in-Particle (PIP)", which is a strong candidate of cancer treatment because of its "theranostic (therapy + diagnostics)" advantages including imaging (e.g., CT) and therapeutic hyperthermia application. In this review, we will elaborate on the current application of theranostic by nanoconfinement. Then, we will narrow down the gold nanoparticle-mediated theranostic application and its nanoconfinement advantages. Finally, the future direction for maximum nanoconfinement mediated cancer therapy will be included.

Cancer gene therapy mediated by RALA/plasmid DNA vectors: Nitrogen to phosphate groups ratio (N/P) as a tool for tunable transfection efficiency and apoptosis

Cancer gene therapy based on p53 tumor suppressor gene supplementation emerges as one of the most challenging and promising strategies. The development of a suitable gene delivery system is imperative to ensure the feasibility and viability of cancer gene therapy in a clinical setting. The conception of delivery systems based on cell- penetrating peptides may deeply contribute for the evolution of therapy efficacy. In this context, the present work explores the p53 encoding plasmid DNA (pDNA) condensation ability of RALA peptide to produce a suitable intracellular delivery platform. These carriers, formed at several nitrogen to phosphate groups (N/P) ratio, were characterized in terms of morphology, size, surface charges, loading and complexation capacity and the fine structure has been analyzed by Fourier-transformed infrared (FTIR) spectroscopy. Confocal microscopy studies confirmed intracellular localization of nanoparticles, resulting in enhanced sustained pDNA uptake. Moreover, in vitro transfection of HeLa cells mediated by RALA/pDNA vectors allows for gene release and p53 protein expression. From these progresses, apoptosis in cancer cells has been investigated. It was found that N/P ratio strongly tailors gene transfection efficiency and, thus, it can be fine-tuned for desired degree of both protein expression and apoptosis. The great asset of the proposed system relies precisely on the use of N/P ratio as a tailoring parameter that can not only modulate vector´s properties but also the extent of pDNA delivery, protein expression and, consequently, the efficacy of p53 mediated cancer therapy.