Nanoencapsulation of a Far-Red Absorbing Phthalocyanine into Poly(benzylmalate) Biopolymers and Modulation of Their Photodynamic Efficiency.

Two different poly(benzylmalate) biopolymers, a hydrophobic non-PEGylated (PMLABe73) and an amphiphilic PEGylated derivative (PEG42-b-PMLABe73), have been used to encapsulate a phthalocyanine chosen for its substitution pattern that is highly suitable for photodynamic therapy. Different phthalocyanine/(co)polymers ratios have been used for the nanoprecipitation. A set of six nanoparticles has been obtained. If the amphiphilic PEGylated copolymer proved to be slightly more efficient for the encapsulation and to lower the aggregation of the phthalocyanine inside the nanoparticles, it is, however, the hydrophobic PMLABe73-based nanoparticles that exhibited the best photodynamic efficiency.

Therapeutic antibody engineering for efficient targeted degradation of membrane proteins in lysosomes.

Targeted degradation of pathological proteins is a promising approach to enhance the effectiveness of therapeutic monoclonal antibodies (mAbs) in cancer therapy. In this study, we demonstrate that this objective can be efficiently achieved by the grafting of mannose 6-phosphate analogues called AMFAs2 onto the therapeutic antibodies trastuzumab and cetuximab, both directed against membrane antigens. The grafting of AMFAs confers to these antibodies the novel property of being internalized via the mannose 6-phosphate receptor (M6PR) pathway. AMFA conjugation to these mAbs significantly increases their cellular uptake and leads to enhanced degradation of the target antigens in cancer cells. This results in a drastic inhibition of cancer cell proliferation compared to unconjugated mAbs, as demonstrated in various cancer cell lines, and an increased therapeutic efficacy in mouse and zebrafish xenografted models. These findings highlight the potential of this technology to improve therapeutic outcomes in cancer treatment.

Engineered therapeutic antibodies with mannose 6-phosphate analogues as a tool to degrade extracellular proteins.

Inducing the degradation of pathological soluble antigens could be the key to greatly enhancing the efficacy of therapeutic monoclonal antibodies (mAbs), extensively used in the treatment of autoimmune and inflammatory disorders or cancer. Lysosomal targeting has gained increasing interest in recent years due to its pharmaceutical applications far beyond the treatment of lysosomal diseases, as a way to address proteins to the lysosome for eventual degradation. Mannose 6-phosphonate derivatives (M6Pn), called AMFA, are unique glycovectors that can significantly enhance the cellular internalization of the proteins conjugated to AMFA via the cation-independent mannose 6-phosphate receptor (M6PR) pathway. AMFA engineering of mAbs results in the generation of a bifunctional antibody that is designed to bind both the antigen and the M6PR. The improvement of the therapeutic potential by AMFA engineering was investigated using two antibodies directed against soluble antigens: infliximab (IFX), directed against tumor necrosis factor α (TNF-α), and bevacizumab (BVZ), directed against the vascular endothelial growth factor (VEGF). AMFA conjugations to the antibodies were performed either on the oligosaccharidic chains of the antibodies or on the lysine residues. Both conjugations were controlled and reproducible and provided a novel affinity for the M6PR without altering the affinity for the antigen. The grafting of AMFA to mAb increased their cellular uptake through an M6PR-dependent mechanism. The antigens were also 2.6 to 5.7 times more internalized by mAb-AMFA and rapidly degraded in the cells. Additional cell culture studies also proved the significantly higher efficacy of IFX-AMFA and BVZ-AMFA compared to their unconjugated counterparts in inhibiting TNF-α and VEGF activities. Finally, studies in a zebrafish embryo model of angiogenesis and in xenografted chick embryos showed that BVZ-AMFA was more effective than BVZ in reducing angiogenesis. These results demonstrate that AMFA grafting induces the degradation of soluble antigens and a significant increase in the therapeutic efficacy. Engineering with mannose 6-phosphate analogues has the potential to develop a new class of antibodies for autoimmune and inflammatory diseases.

Probing the Use of Triphenyl Phosphonium Cation for Mitochondrial Nucleoside Delivery.

Herein, we report the design, the synthesis, and the study of novel triphenyl phosphonium-based nucleoside conjugates. 2'-Deoxycytidine was chosen as nucleosidic cargo, as it allows the introduction of fluorescein on the exocyclic amine of the nucleobase and grafting of the vector was envisaged through the formation of a biolabile ester bond with the hydroxyl function at the 5'-position. Compound 3 was identified as a potential nucleoside prodrug, showing ability to be internalized efficiently into cells and to be co-localized with mitochondria.

Exceptional anticancer photodynamic properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II).

Phthalocyanines have been described as effective photosensitizers for photodynamic therapy and are therefore, being studied for their biomedical applications. The metalation of photosensitizers can improve their photodynamic therapy potential. Here, we focus on the biological properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II) (ZnPc(αEG4)2) and demonstrate its exceptional anticancer activity upon light stimulation to kill preferentially cancer cells with a start of efficiency at 10 pM. Indeed, in this work we highlighted the high selectivity of ZnPc(αEG4)2 for cancer cells compared with healthy ones and we establish its mechanism of action, enabling us to conclude that ZnPc(αEG4)2 could be a powerful tool for cancer therapy.

Novel Antifouling Coatings by Zwitterionic Silica Grafting on Glass Substrates.

Zwitterionic silica coatings for surface functionalization are greatly prominent because of their simple and fast preparation, high availability, and effective antifouling properties. In this work, two zwitterionic sulfobetaine silane coatings, i.e., mono-SBSi and tris-SBSi, were deposited on glass surfaces and tested for antifouling of biological material and biofilm using human cancer cell and seawater, respectively. The used zwitterionic precursors mono-SBSi and tris-SBSi differ by the number of hydrolyzable silane groups: mono-SBSi contains one trimethoxysilane group, whereas tris-SBSi contains three of these functions. First, X-ray photoelectron spectroscopy indicates the successful grafting of zwitterionic coatings onto a glass surface. Characterization using atomic force microscopy shows the different morphologies and roughness of the two coatings. The glass surface became more hydrophilic after the grafting of zwitterionic coatings than the bare glass substrate. The antifouling properties of two coatings were evaluated via human cancer cell adsorption. Interestingly, the tris-SBSi coating displays a significantly lower level of cell adsorption compared to that of both mono-SBSi coating and the non-modified control surface. The same trend was observed for biofilm formation in seawater. Finally, the toxicity of mono-SBSi and tris-SBSi coatings was evaluated on zebrafish embryos, indicating the good biocompatibility of both coatings. Our results indicate interesting antifouling properties of zwitterionic coatings. The chemical constitution of the used precursor has an impact on the antifouling properties of the formed coating: the tris-SBSi-based zwitterionic silica coatings display improved antifouling properties compared to those of the mono-SBSi-based coating. Besides, the use of trisilylated precursors should result in the formation of more resistant and robust coatings due to the higher number of grafting functions. For all these reasons, we anticipate that tris-SBSi coatings will open new perspectives for antifouling applications for biological environments and implants.

Cation-independent mannose 6-phosphate receptor: From roles and functions to targeted therapies.

The cation-independent mannose 6-phosphate receptor (CI-M6PR) is a ubiquitous transmembrane receptor whose main intracellular role is to direct enzymes carrying mannose 6-phosphate moieties to lysosomal compartments. Recently, the small membrane-bound portion of this receptor has appeared to be implicated in numerous pathophysiological processes. This review presents an overview of the main ligand partners and the roles of CI-M6PR in lysosomal storage diseases, neurology, immunology and cancer fields. Moreover, this membrane receptor has already been noted for its strong potential in therapeutic applications thanks to its cellular internalization activity and its ability to address pathogenic factors to lysosomes for degradation. A number of therapeutic delivery approaches using CI-M6PR, in particular with enzymes, antibodies or nanoparticles, are currently being proposed.

Upscale Synthesis of Magnetic Mesoporous Silica Nanoparticles and Application to Metal Ion Separation: Nanosafety Evaluation.

The synthesis of core-shell magnetic mesoporous nanoparticles (MMSNs) through a phase transfer process is usually performed at the 100-250 mg scale. At the gram scale, nanoparticles without cores or with multicore systems are observed. Iron oxide core nanoparticles (IO) were synthesized through a thermal decomposition procedure of α-FeO(OH) in oleic acid. A phase transfer from chloroform to water was then performed in order to wrap the IO nanoparticles with a mesoporous silica shell through the sol-gel procedure. MMSNs were then functionalized with DTPA (diethylenetriaminepentacetic acid) and used for the separation of metal ions. Their toxicity was evaluated. The phase transfer procedure was crucial to obtaining MMSNs on a large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. The homogeneous dispersion of MMSNs on the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPAs were shown to have a strong affinity for Ni ions. Furthermore, toxicity was evaluated in cells, zebrafish and seahorse cell metabolic assays, and the nanoparticles were found to be nontoxic. We developed a method of preparing MMSNs at the gram scale. After functionalization with DTPA, the nanoparticles were efficient in metal ion removal and separation; furthermore, no toxicity was noticed up to 125 µg mL-1 in zebrafish.

Hybrid multifunctionalized mesostructured stellate silica nanoparticles loaded with ß-diketonate Tb3+/Eu3+ complexes as efficient ratiometric emissive thermometers working in water.

Despite the great effort made in recent years on lanthanide-based ratiometric luminescent nanothermometers able to provide temperature measurements in water, their design remains challenging. We report on the synthesis and properties of efficient ratiometric nanothermometers that are based on mesoporous stellate nanoparticles (MSN) of ca. 90 nm functionalized with an acetylacetonate (acac) derivative inside the pores and loaded with ß-diketonate-Tb3+/Eu3+ complexes able to work in water, in PBS or in cells. Encapsulating a [(Tb/Eu)9(acac)16(µ3-OH)8(µ4-O)(µ4-OH)] complex (Tb/Eu ratio = 19/1 and 9/1) led to hybrid multifunctionalized nanoparticles exhibiting a Tb3+ and Eu3+ characteristic temperature-dependent luminescence with a high rate Tb3+-to-Eu3+ energy transfer. According to theoretical calculations, the modifications of photoluminescence properties and the increase in the pairwise Tb3+-to-Eu3+ energy transfer rate by about 10 times can be rationalized as a change of the coordination number of the Ln3+ sites of the complex from 7 to 8 accompanied by a symmetry evolution from Cs to C4v and a slight shortening of intramolecular Ln3+-Ln3+ distances upon the effect of encapsulation. These nanothermometers operate in the 20-70 °C range with excellent photothermal stability, cyclability and repeatability (>95%), displaying a maximum relative thermal sensitivity of 1.4% °C-1 (at 42.7 °C) in water. Furthermore, they can operate in cells with a thermal sensitivity of 8.6% °C-1 (at 40 °C), keeping in mind that adjusting the calibration for each system is necessary to ensure accurate measurements.

Novel Biocompatible Trianglamine Networks for Efficient Iodine Capture.

Herein, we report for the first time a biocompatible cross-linked trianglamine (Δ) network for the efficient iodine removal from the vapor phase, water, and seawater. In the vapor phase, the cross-linked network could capture 6 g g-1 of iodine, ranking among the most performant materials for iodine vapor capture. In the liquid phase, this cross-linked network is also capable of capturing iodine at high rates from aqueous media (water and seawater). This network displayed fast adsorption kinetics, and they are fully recyclable. This study reveals the high affinity of iodine for the intrinsic cavity of the trianglamine. The synthesized materials are extremely interesting since they are environmentally friendly and inexpensive and the synthesis could easily be scaled up to be used as the material of choice in response to accidents in the nuclear industry.

Super-resolution imaging of antibody-conjugated biodegradable periodic mesoporous organosilica nanoparticles for targeted chemotherapy of prostate cancer.

Biodegradable periodic mesoporous organosilica nanoparticles (nanoPMOs) are widely used as responsive drug delivery platforms for targeted chemotherapy of cancer. However, the evaluation of their properties such as surface functionality and biodegradability is still challenging, which has a significant impact on the efficiency of chemotherapy. In this study, we have applied direct stochastic optical reconstruction microscopy (dSTORM), a single-molecule super-resolution microscopy technique, to quantify the degradation of nanoPMOs triggered by glutathione and the multivalency of antibody-conjugated nanoPMOs. Subsequently, the effect of these properties on cancer cell targeting, drug loading and release capability, and anticancer activity is also studied. Due to the higher spatial resolution at the nanoscale, dSTORM imaging is able to reveal the structural properties (i.e., size and shape) of fluorescent and biodegradable nanoPMOs. The quantification of nanoPMOs' biodegradation using dSTORM imaging demonstrates their excellent structure-dependent degradation behavior at a higher glutathione concentration. The surface functionality of anti-M6PR antibody-conjugated nanoPMOs as quantified by dSTORM imaging plays a key role in prostate cancer cell labeling: oriented antibody is more effective than random ones, while high multivalency is also effective. The higher biodegradability and cancer cell-targeting properties of nanorods conjugated with oriented antibody (EAB4H) effectively deliver the anticancer drug doxorubicin to cancer cells, exhibiting potent anticancer effects.

Dendritic Mesoporous Organosilica Nanoparticles with Photosensitizers for Cell Imaging, siRNA Delivery and Protein Loading.

Dendritic mesoporous organosilica nanoparticles (DMON) are a new class of biodegradable nanoparticles suitable for biomolecule delivery. We studied the photochemical internalization (PCI) and photodynamic therapy (PDT) of DMON to investigate new ways for DMON to escape from the endosomes-lysosomes and deliver biomolecules into the cytoplasm of cells. We added photosensitizers in the framework of DMON and found that DMON were loaded with siRNA or FVIII factor protein. We made four formulations with four different photosensitizers. The photosensitizers allowed us to perform imaging of DMON in cancer cells, but the presence of the tetrasulfide bond in the framework of DMON quenched the formation of singlet oxygen. Fortunately, one formulation allowed us to efficiently deliver proapoptotic siRNA in MCF-7 cancer cells leading to 31% of cancer cell death, without irradiation. As for FVIII protein, it was loaded in two formulations with drug-loading capacities (DLC) up to 25%. In conclusion, DMON are versatile nanoparticles capable of loading siRNA and delivering it into cancer cells, and also loading FVIII protein with good DLC. Due to the presence of tetrasulfide, it was not possible to perform PDT or PCI.

Two-Photon Light Trigger siRNA Transfection of Cancer Cells Using Non-Toxic Porous Silicon Nanoparticles.

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES-azo@Lys) to efficiently complex siRNA. Non-linear excitation of the two-photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene-siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF-7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF-7 cancer cell death. The developed technique using two-photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation.

Superparamagnetic Spinel-Ferrite Nano-Adsorbents Adapted for Hg2+, Dy3+, Tb3+ Removal/Recycling: Synthesis, Characterization, and Assessment of Toxicity.

In the present work, superparamagnetic adsorbents based on 3-aminopropyltrimethoxy silane (APTMS)-coated maghemite (γFe2O3@SiO2-NH2) and cobalt ferrite (CoFe2O4@SiO2-NH2) nanoparticles were prepared and characterized using transmission-electron microscopy (TEM/HRTEM/EDXS), Fourier-transform infrared spectroscopy (FTIR), specific surface-area measurements (BET), zeta potential (ζ) measurements, thermogravimetric analysis (TGA), and magnetometry (VSM). The adsorption of Dy3+, Tb3+, and Hg2+ ions onto adsorbent surfaces in model salt solutions was tested. The adsorption was evaluated in terms of adsorption efficiency (%), adsorption capacity (mg/g), and desorption efficiency (%) based on the results of inductively coupled plasma optical emission spectrometry (ICP-OES). Both adsorbents, γFe2O3@SiO2-NH2 and CoFe2O4@SiO2-NH2, showed high adsorption efficiency toward Dy3+, Tb3+, and Hg2+ ions, ranging from 83% to 98%, while the adsorption capacity reached the following values of Dy3+, Tb3+, and Hg2+, in descending order: Tb (4.7 mg/g) > Dy (4.0 mg/g) > Hg (2.1 mg/g) for γFe2O3@SiO2-NH2; and Tb (6.2 mg/g) > Dy (4.7 mg/g) > Hg (1.2 mg/g) for CoFe2O4@SiO2-NH2. The results of the desorption with 100% of the desorbed Dy3+, Tb3+, and Hg2+ ions in an acidic medium indicated the reusability of both adsorbents. A cytotoxicity assessment of the adsorbents on human-skeletal-muscle derived cells (SKMDCs), human fibroblasts, murine macrophage cells (RAW264.7), and human-umbilical-vein endothelial cells (HUVECs) was conducted. The survival, mortality, and hatching percentages of zebrafish embryos were monitored. All the nanoparticles showed no toxicity in the zebrafish embryos until 96 hpf, even at a high concentration of 500 mg/L.

Development of targeted photodynamic therapy drugs by combining a zinc phthalocyanine sensitizer with TSPO or EGFR binding groups: the impact of the number of targeting agents on biological activity.

Drug-targeted delivery has become a top priority in the world of medicine in order to develop more efficient therapeutic agents. This is important as a critical underlying problem in cancer therapy stems from the inability to deliver active therapeutic substances directly to tumor cells without causing collateral damage. In this work, zinc(II) phthalocyanine (ZnPc) was selected as a sensitizer and was linked to different targeting agents, which would be recognized by overexpressed proteins in cancer cells. As targeting agents, we first selected the two ligands (DAA1106, PK11195) of the translocator protein (TSPO) and then Erlotinib a binding group of the ATP domain of tyrosine kinase in epidermal growth factor (EGFR). ZnPc was connected via an ethylene glycol chain to either one (n = 1) or four (n = 4) targeting agents. The biological activity of these conjugates ZnPc(ligand)n was investigated on MDA-MB-231 breast human cancer cells and human hepatoma HepG2 cells, first in the dark (cytotoxicity) and then under irradiation (photodynamic therapy). The dark cytotoxicity was extremely low (IC50 ≥ 50 µM) for all of these compounds, which is a required criterion for further photodynamic application. After irradiation at 650 nm, only the conjugates bearing one targeting ligand such as ZnPc-[DAA1106]1, ZnPc-[PK11195]1, and ZnPc-[Erlo]1 showed photodynamic activity, while those linked to 4 targeting agents were inactive. Importantly, fluorescence imaging microscopy showed the colocalization of ZnPc-[DAA1106]1, ZnPc-[PK11195]1 and ZnPc-[erlo]1, at mitochondria, a result that justifies the observed photodynamic activity of these conjugates. This study first shows the impact of the number and the mode of organization of targeting agents on the ability of the sensitizer to cross the cell membrane. When zinc(II) phthalocyanine carries a single targeting agent, a significant photodynamic activity on MDA-MB-231 breast human cancer cells was measured and localization at the mitochondria was demonstrated by fluorescence imaging, thus proving the potential of the sensitizer linked to a targeting agent to improve selectivity. Another important conclusion from this study for the design of future effective PDT drugs using multivalence effects is to control the arrangement of the targeting agents in order to design molecules that will be able to pass the cell membrane barriers.

Mannose 6-phosphate receptor-targeting antibodies preserve Fc receptor-mediated recycling.

The concept of grafting mannose 6-phosphonate derivatives (M6Pn), named AMFA, on therapeutic proteins was first developed for the improvement of enzyme delivery in lysosomal storage disorders. This glycoengineering increases the cellular uptake of the protein via the cation-independent mannose 6-phosphate receptor (M6PR) which further allows their targeting to the lysosomes. In the present study, we investigated the extent to which the direct grafting of AMFA onto a drug, here a monoclonal antibody (mAb), affects the cell uptake and recycling of the antibody. The antibodies infliximab (IFX) and adalimumab (ADA), directed against the tumor necrosis factor α (TNFα), grafted with AMFA acquired an affinity for the M6PR, resulting in a >3-fold increase in drug release in cells. Subsequently, the impact of AMFA grafting to the Fc portion of mAb on its affinity for the neonatal Fc receptor (FcRn), which is the key receptor for antibody recycling, was evaluated. Whether one to three AMFA moieties were grafted, FcRn-mediated recycling of mAb was not affected. AMFA grafting did not impair the pharmacokinetics of both ADA and IFX and presented a high stability since AMFA were still bound to mAb in the plasma of mice 21 days after the treatment. In conclusion, this type of antibody engineering with a reduced number of AMFA confers M6PR targeting property and increases endocytosis, and yet appears fully compatible with FcRn binding and with antibody recycling and transcytosis.

Special Issue "Nanoplatforms Based Cancers Therapy".

Nanomedicine is now considered a hopeful strategy to efficiently target cancer cells and deliver, more specifically, the molecule of interest to the area to image and treat cells [...].

Photosensitivity of Different Nanodiamond-PMO Nanoparticles in Two-Photon-Excited Photodynamic Therapy.

BACKGROUND: In addition to their great optical properties, nanodiamonds (NDs) have recently proved useful for two-photon-excited photodynamic therapy (TPE-PDT) applications. Indeed, they are able to produce reactive oxygen species (ROS) directly upon two-photon excitation but not with one-photon excitation; Methods: Fluorescent NDs (FNDs) with a 100 nm diameter and detonation NDs (DNDs) of 30 nm were compared. In order to use the gems for cancer-cell theranostics, they were encapsulated in a bis(triethoxysilyl)ethylene-based (ENE) periodic mesoporous organosilica (PMO) shell, and the surface of the formed nanoparticles (NPs) was modified by the direct grafting of polyethylene glycol (PEG) and amino groups using PEG-hexyltriethoxysilane and aminoundecyltriethoxysilane during the sol-gel process. The NPs' phototoxicity and interaction with MDA-MB-231 breast cancer cells were evaluated afterwards; Results: Transmission electronic microscopy images showed the formation of core-shell NPs. Infrared spectra and zeta-potential measurements confirmed the grafting of PEG and NH2 groups. The encapsulation of the NDs allowed for the imaging of cancer cells with NDs and for the performance of TPE-PDT of MDA-MB-231 cancer cells with significant mortality. CONCLUSIONS: Multifunctional ND@PMO core-shell nanosystems were successfully prepared. The NPs demonstrated high biocompatibility and TPE-PDT efficiency in vitro in the cancer cell model. Such systems hold good potential for two-photon-excited PDT applications.

D-Mannose-appended 5,15-diazaporphyrin for photodynamic therapy.

5,15-Diazaporphyrin appended with D-mannose moieties was prepared through Suzuki-Miyaura cross-coupling reaction and SN2 alkylation. The resultant diazaporphyrin was hydrophilic enough to exhibit sufficient solubility in aqueous media. Because of the photosensitizing ability of diazaporphyrins, the in vitro activity of the D-mannose-appended diazaporphyrin in photodynamic therapy (PDT) was investigated. The specific internalization of the functionalized diazaporphyrin into human breast adenocarcinoma (MDA-MB-231) cells through mannose receptors was confirmed by confocal microscopy imaging. We also demonstrated the strong PDT activity of the functionalized diazaporphyrin at a nanomolar level with short light irradiation time.

Photochemical Internalization of siRNA for Cancer Therapy.

In the race to design ever more effective therapy with ever more focused and controlled actions, nanomedicine and phototherapy seem to be two allies of choice. Indeed, the use of nanovectors making it possible to transport and protect genetic material is becoming increasingly important. In addition, the use of a method allowing the release of genetic material in a controlled way in space and time is also a strategy increasingly studied thanks to the use of lasers. In parallel, the use of interfering RNA and, more particularly, of small-interfering RNA (siRNA) has demonstrated significant potential for gene therapy. In this review, we focused on the design of the different nanovectors capable of transporting siRNAs and releasing them so that they can turn off the expression of deregulated genes in cancers through controlled photoexcitation with high precision. This mechanism, called photochemical internalization (PCI), corresponds to the lysosomal leakage of the cargo (siRNA in this case) after destabilization of the lysosomal membrane under light excitation.