Theranostic Tool Research Articles

Quantum dots as a theranostic approach in Alzheimer's disease: a systematic review.

Aim: Quantum dots (QDs) are nanoparticles that have an emerging application as theranostic agents in several neurodegenerative diseases. The advantage of QDs as nanomedicine is due to their unique optical properties that provide high sensitivity, stability and selectivity at a nanoscale range. Objective: To offer renewed insight into current QD research and elucidate its promising application in Alzheimer's disease (AD) diagnosis and therapy. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar databases that included the following search terms: 'quantum dots', 'blood-brain barrier', 'cytotoxicity', 'toxicity' and 'Alzheimer's disease'; PRISMA guidelines were adhered to. Results: Thirty-four publications were selected to evaluate the ability of QDs to cross the blood-brain barrier, potential toxicity and current AD diagnostic and therapeutic applications. Conclusion: QD's unique optical properties and versatility to conjugate to various biomolecules, while maintaining a nanoscale size, render them a promising theranostic tool in AD.

Increased lipid peroxidation by graphene quantum dots induces ferroptosis in macrophages

Graphene quantum dots (GQDs) are an excellent tool for theranostics, and are widely used in nanomedical applications. The biosafety of GQDs has received abundant attention, but their latent toxicological mechanisms remain inadequately understood. To investigate the cellular and molecular mechanisms underlying graphene-mediated changes, quantitative proteomics and untargeted lipidomics were integrated. We discovered that glutathione peroxidase 4 as a key regulator of ferroptosis, was down-regulated at the protein level by GQDs. Lipidomics profiling with features of ferroptosis was identified in GQDs-treated RAW264.7 macrophages. Furthermore, GQDs exposure was associated with reduced levels of GSH and increased lipid peroxidation. Overexpression of GPX4 in RAW264.7 cells and pre-treatment of a ferroptosis inhibitor Ferrostatin-1 (Fer-1) not only suppressed cell death, but also alleviated lipid peroxidation. Taken together, our results indicated that GQDs exposure induced ferroptosis in RAW264.7 macrophages, and provided essential data for biosafety evaluations of GQDs.

A strand-elongation initiated DNAzyme walker for terminal deoxynucleotidyl transferase activity detection

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase found to be overactive in most leukemia cells and is recognized as a biomarker of leukemia. Here, we develop a strand-elongation initiated DNAzyme walker to detect TdT activity. The walker is constructed by modifying specially designed track strand (TS) and incomplete walking strand (WS) onto the surface of a mesoporous silica nanoparticle (MSN) loaded with large amounts of rhodamine 6 G (Rh6 G) in its pores. The TS is a hairpin DNA with an RNA cleavage site, serving as substrate for DNAzyme and encapsulating the Rh6 G. The incomplete WS contains one side of binding arm and partial catalytic core of DNAzyme. Under the action of TdT, the incomplete WS is elongated with polyA, completing the lacking part of catalytic core and the other side of binding arm of DNAzyme. Then the completed DNAzyme cleave the TSs, unblocking and releasing the Rh6 G to indicate the TdT activity. This walker is completed and initiated only after the action of TdT, ensuring its strict specificity for TdT activity. Besides, each WS cleave multiple TSs, and each cleavage leads massive Rh6 G to be released. Such double-amplified signal accumulation endows the walker with good sensitivity. This walker specifically detected TdT activity down to 0.093 U mL−1, and successfully detected TdT activity in human serum. The proposed walker demonstrates a novel method for specific and sensitive detection of TdT activity, providing an effective tool for TdT-related biological research and leukemia theranostics.

Silver Nanoparticles Decorated with PEGylated Porphyrins as Potential Theranostic and Sensing Agents.

Silver nanoparticles (AgNPs) stand out over other metal nanoparticles thanks to their peculiar bactericidal and spectroscopic properties. Tunability of the AgNPs chemical–physical properties could be provided through their organic covalent coating. On the other hand, PEGylated porphyrin derivatives are versatile heteromacrocycles investigated for uses in the biomedical field as cytotoxic and tracking agents, but also as sensors. In this work, an easy multi-step approach was employed to produce coated silver nanoparticles. Specifically, the AgNPs were functionalized with 5,10,15-[p-(ω-methoxy-polyethyleneoxy)phenyl]-20-(p-hydroxyphenyl)-porphyrin (P(PEG350)3), using chloropropanethiol as a coupling agent. The P(PEG350)3 was structurally characterized through MALDI-TOF mass spectrometry, NMR spectroscopy and thermal analyses. The functionalization of AgNPs was monitored step-by-step employing UV-Vis spectroscopy, dynamic light scattering and thermogravimetric techniques. HRTEM and STEM measurements were used to investigate the morphology and the composition of the resulting nanostructured system (AgNP@P(PEG350)3), observing a long-range alignment of the outer porphyrin layer. The AgNP@P(PEG350)3 combines the features of the P(PEG350)3 with those of AgNPs, producing a potential multifunctional theranostic tool. The nanosystem revealed itself suitable as a removable pH sensor in aqueous solutions and potentially feasible for biological environment applications.

Functionalization of Metal and Carbon Nanoparticles with Potential in Cancer Theranostics.

Cancer theranostics is a new concept of medical approach that attempts to combine in a unique nanoplatform diagnosis, monitoring and therapy so as to provide eradication of a solid tumor in a non-invasive fashion. There are many available solutions to tackle cancer using theranostic agents such as photothermal therapy (PTT) and photodynamic therapy (PDT) under the guidance of imaging techniques (e.g., magnetic resonance—MRI, photoacoustic—PA or computed tomography—CT imaging). Additionally, there are several potential theranostic nanoplatforms able to combine diagnosis and therapy at once, such as gold nanoparticles (GNPs), graphene oxide (GO), superparamagnetic iron oxide nanoparticles (SPIONs) and carbon nanodots (CDs). Currently, surface functionalization of these nanoplatforms is an extremely useful protocol for effectively tuning their structures, interface features and physicochemical properties. This approach is much more reliable and amenable to fine adjustment, reaching both physicochemical and regulatory requirements as a function of the specific field of application. Here, we summarize and compare the most promising metal- and carbon-based theranostic tools reported as potential candidates in precision cancer theranostics. We focused our review on the latest developments in surface functionalization strategies for these nanosystems, or hybrid nanocomposites consisting of their combination, and discuss their main characteristics and potential applications in precision cancer medicine.

A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis.

Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe−/− mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications.

A quantitative analysis of total and free 11-oxygenated androgens and its application to human serum and plasma specimens using liquid-chromatography tandem mass spectrometry

Bioactive 11-oxygenated C19 adrenal-derived steroids (11-oxy C19) are potentially relevant in diverse endocrine and metabolic contexts. We report the development and validation of a liquid chromatography electrospray ionization tandem mass spectrometric method (LC-ESI-MS/MS) for the simultaneous quantification of seven 11-oxy C19 using 200 µL of plasma or serum. Sample preparation involved chemical derivatization using hydroxylamine after liquid–liquid extraction to improve specificity and sensitivity. The method allowed the quantitation of total 11-oxy C19 (free + sulfate and glucuronide conjugates) following enzymatic hydrolysis. This included the abundant precursor 11-hydroxyandrostenedione (11OHA4) and the most potent androgenic derivatives 11-keto-testosterone (11KT) and 11-keto-dihydrotestosterone (11KDHT), their abundant metabolites 11-hydroxyandrosterone (11OHAST) and 11-keto-androsterone (11KAST) potentially feeding back into the pool of potent androgens, in addition to 11-keto-androstenedione (11KA4) and 11-hydroxytestosterone (11OHT). Stable isotopes were used as internal standards, and calibrators and quality controls were prepared in the same matrix as the study samples. Performance was validated against the Food and Drug Administration Criteria. The method was sensitive with lower limit of quantification (LLOQ) values of 10 and 20 pg/mL for free and total 11-oxy C19, respectively. The applicability was demonstrated in men and women adult donors that showed sex-differences. All steroids were quantified well above LLOQ, except 11KDHT that remained undetectable suggesting interfering endogenous molecules present in non-derivatized samples in which a peak was observed. By providing accurate and reliable quantitative data, this method will permit to evaluate how profiling of 11-oxy C19 will be most informative as diagnostic, prognostic and/or theranostic tools.

Self-Assembled Hybrid Nanogel as a Multifunctional Theranostic Probe for Enzyme-Regulated Ultrasound Imaging and Tumor Therapy.

Multifunctional theranostic nanoprobes integrated with stimuli-responsive imaging and therapeutic capabilities have shown great potential to enhance the early cancer diagnostic efficacy and therapeutic efficiency. Elevated levels of lactate and hydrogen peroxide have been considered as the characteristic feature of the tumor microenvironment and can thus be exploited for developing promising theranostic strategies. We demonstrate here that the biocompatible and responsive enzyme-based nanogel probe has been designed as a promising theranostic tool to target high lactate and hydrogen peroxide for ultrasound imaging (US) and cancer treatment. We encapsulate the dual enzyme lactate oxidase (LOD) and catalase (CAT) into the self-assembled nanogels to fabricate responsive nanoprobe LOD/CAT-loaded nanogels (LCNGs). The nanoprobes can respond to the lactate and H2O2 rich tumor microenvironment to generate abundant oxygen, which further accumulates into microbubbles for enhanced US imaging. Besides, LCNGs@DOX has been further created by integrating the nanoprobes with doxorubicin (DOX) for cancer therapy. Both in vitro and in vivo results demonstrate enhanced US imaging and effective cell proliferation inhibition of LCNGs@DOX, allowing the preparation of safe and efficient theranostic nanoprobes capable of responsive US imaging and treating tumors.

Emerging photoacoustic and thermoacoustic imaging technologies for detecting primary and metastatic cancer and guiding therapy.

In recent years, there has been a progressive trend towards less invasive technologies for detecting metastatic cancer and guiding therapy with the goal of lower morbidity, better outcomes, and superior cosmetic appearance than traditional methods. This mini-review examines three emerging noninvasive hybrid technologies for detecting primary cancer, metastasis and guiding thermal therapy. Real-time thermoacoustic imaging and thermometry potentially provides valuable and critical feedback for guiding focused microwave ablation therapy. Label-free photoacoustic monitoring of cancer cells is a promising clinical diagnostic and theranostic tool for detecting metastatic disease and monitoring the response to therapy. Finally, immunologically targeted gold nanoparticles combined with photoacoustic imaging is able to detect lymph node micrometastasis in mouse models of breast cancer. These emerging techniques have the potential to improve the decision to biopsy, provide more accurate prognosis, and enhance the efficacy of therapy for early and late stage cancers.

Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers both central and peripheral inflammatory responses. Existing pharmacological drugs are unable to effectively and quickly target the brain inflamed regions, setting up a major roadblock towards effective brain trauma treatments. Nanoparticles (NPs) have been used in multiple diseases as drug delivery tools with remarkable success due to their rapid diffusion and specificity in the target organ. Here, leukocyte‐based biomimetic NPs are fabricated as a theranostic tool to directly access inflamed regions in a TBI mouse model. This NP systemic delivery is visualized using advanced in vivo imaging techniques, including intravital microscopy and in vivo imaging system. The results demonstrate selective targeting of NPs to the injured brain and increased NPs accumulation among the peripheral organs 24 h after TBI. Interestingly, increased microglial proliferation, decreased macrophage infiltration, and reduced brain lesion following the NPs treatments compared to sham vehicle‐treated mice are also found. In summary, the results suggest that NPs represent a promising future theranostic tool for TBI treatment.

Towards the development of antioxidant-wrapped graphene-based fluorescent nanomaterials having theranostic potentials: A combined experimental and theoretical study

We report here an easily implementable, economic and eco-friendly synthetic protocol for the antioxidant (DMAHF/DHF, 3-hydroxyflavone analogs)-wrapped fluorescent graphene oxide (GO). The antioxidant activity of DMAHF was further exploited to reduce GO; whereby DMAHF was oxidized. The mechanistic pathway of this rGO (reduced GO)-synthesis and its consequence on the fate of DMAHF; as well as the origin of spectral behavior of GO/rGO nanohybrid systems were understood by quantum chemical calculations and molecular docking studies. The GO/rGO-surface anchored (non-covalently) fluorescent antioxidant molecules (either in their native/oxidized forms) imposed characteristic fluorophoric nature to these nanohybrid systems. However, such interactions instigated a simultaneous quenching of the fluorescence of these molecules to some extent. Interestingly, the fluorescence of these nanohybrid systems was found to be largely enhanced in the presence of the biomolecules, like dsDNA (ctDNA). This was the basis of their activity as fluoroprobes for dsDNA. Being loaded with the bio-friendly antioxidant molecules, these nanohybrids can be potentially biocompatible. Thus, these graphene based nanohybrids with dsDNA-fluoroprobing efficacy and significant structural advantages can be promising candidates for the future development of advanced theranostic tools.

Crystallization, Luminescence and Cytocompatibility of Hexagonal Calcium Doped Terbium Phosphate Hydrate Nanoparticles.

Luminescent lanthanide-containing biocompatible nanosystems represent promising candidates as nanoplatforms for bioimaging applications. Herein, citrate-functionalized calcium-doped terbium phosphate hydrate nanophosphors of the rhabdophane type were prepared at different synthesis times and different Ca2+/Tb3+ ratios by a bioinspired crystallization method consisting of thermal decomplexing of Ca2+/Tb3+/citrate/phosphate/carbonate solutions. Nanoparticles were characterized by XRD, TEM, SEM, HR-TEM, FTIR, Raman, Thermogravimetry, inductively coupled plasma spectroscopy, thermoanalysis, dynamic light scattering, electrophoretic mobility, and fluorescence spectroscopy. They displayed ill-defined isometric morphologies with sizes ≤50 nm, hydration number n ~ 0.9, tailored Ca2+ content (0.42–8.11 wt%), and long luminescent lifetimes (800–2600 µs). Their relative luminescence intensities in solid state are neither affected by Ca2+, citrate content, nor by maturation time for Ca2+ doping concentration in solution below 0.07 M Ca2+. Only at this doping concentration does the maturation time strongly affect this property, decreasing it. In aqueous suspensions, neither pH nor ionic strength nor temperature affect their luminescence properties. All the nanoparticles displayed high cytocompatibility on two human carcinoma cell lines and cell viability correlated positively with the amount of doping Ca2+. Thus, these nanocrystals represent promising new luminescent nanoprobes for potential biomedical applications and, if coupled with targeting and therapeutic moieties, they could be effective tools for theranostics.

Carbon dots and curcumin-loaded CD44-Targeted liposomes for imaging and tracking cancer chemotherapy: A multi-purpose tool for theranostics

Growing needs in biomedical applications have driven the development of multifunctional nanoparticles towards theranostically-engineered multimodal platforms. Many strategies for point-effective cellular uptake of theranostics have been described. In this report, multifunctional nanostructures were designed and synthesized as a novel theranostic platform. Liposomes were loaded with curcumin as a therapeutic agent and carbon dots (CDs) as a contrast molecule. Anti-CD44 antibodies were bioconjugated on the liposomal surface to obtain an active targeting nanocarrier. After synthesis, the relative characterization of the vesicles was performed using DLS and TEM techniques. In vitro analysis was conducted to investigate the multimodal properties of the theranostic via testing its toxicity, cell uptake, bioimaging, and chemo/radiotherapy applications on two different cell lines. 3D holographic microscopy was employed to track the treatment effects during experimentation. Results indicated that these particles are efficient tools for clinical applications due to their fluorescent characteristic and increased bioperformance.

Dendrimer Architectonics to Treat Cancer and Neurodegenerative Diseases with Implications in Theranostics and Personalized Medicine.

Integration of diagnostic and therapeutic functions in a single platform namely theranostics has become a cornerstone for personalized medicine. Theranostics platform facilitates noninvasive detection and treatment while allowing the monitoring of disease progression and therapeutic efficacy in case of chronic conditions of cancer and Alzheimer's disease (AD). Theranostic tools function by themselves or with the aid of carrier, viz. liposomes, micelles, polymers, or dendrimers. The dendrimer architectures (DA) are well-characterized molecular nanoobjects with a large number of terminal functional groups to enhance solubility and offer multivalency and multifunctional properties. Various noninvasive diagnostic tools like magnetic resonance imaging (MRI), computed tomography (CT), gamma scintigraphy, and optical techniques have been accomplished utilizing DAs for simultaneous imaging and drug delivery. Obstacles in the formulation design, drug loading, payload delivery, biocompatibility, overcoming cellular membrane and blood-brain barrier (BBB), and systemic circulation remain a bottleneck in translational efforts. This review focuses on the diagnostic, therapeutic and theranostic potential of DA-based nanocarriers in treating cancer and neurodegenerative disorders like AD and Parkinson's disease (PD), among others. In view of the inverse relationship between cancer and AD, designing suitable DA-based theranostic nanodrug with high selectivity has tremendous implications in personalized medicine to treat cancer and neurodegenerative disorders.

αvβ3-Specific Gold Nanoparticles for Fluorescence Imaging of Tumor Angiogenesis.

This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for αvβ3-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance. Furthermore, the therapeutic properties of the AuNPs were evaluated in vitro on pUC19 DNA and on A431 cells concerning acute and long-term toxicity, indicating that these AuNPs could be useful as radiosensitizers in therapeutic concepts in the future.

Central nervous system delivery of molecules across the blood-brain barrier

Therapies targeting neurological conditions such as Alzheimer's or Parkinson's diseases are hampered by the presence of the blood-brain barrier (BBB). During the last decades, several approaches have been developed to overcome the BBB, such as the use of nanoparticles (NPs) based on biomaterials, or alternative methods to open the BBB. In this review, we briefly highlight these strategies and the most recent advances in this field. Limitations and advantages of each approach are discussed. Combination of several methods such as functionalized NPs targeting the receptor-mediated transcytosis system with the use of magnetic resonance imaging-guided focused ultrasound (FUS) might be a promising strategy to develop theranostic tools as well as to safely deliver therapeutic molecules, such as drugs, neurotrophic factors or antibodies within the brain parenchyma.

Non-invasive multimodal imaging of Diabetic Retinopathy: A survey on treatment methods and Nanotheranostics

Diabetes Retinopathy (DR) is one of the most prominent microvascular complications of diabetes. It is one of the pre-eminent causes for vision impairment followed by blindness among the working-age population worldwide. The de facto cause for DR remains challenging, despite several efforts made to unveil the mechanism underlying the pathology of DR. There is quite less availability of the low cost pre-emptive theranostic imaging tools in terms of in-depth resolution, due to the multiple factors involved in the etiology of DR. This review work comprehensively explores the various reports and research works on all perspectives of diabetic retinopathy (DR), and its mechanism. It also discusses various advanced non-destructive imaging modalities, current, and future treatment approaches. Further, the application of various nanoparticle-based drug delivery strategies used for the treatment of DR are also discussed. In a nutshell, the present review work bolsters the pursuit of the development of an advanced non-invasive optical imaging modal with a nano-theranostic approach for the future diagnosis and treatment of DR and its associated ocular complications.

Review of nanotheranostics for molecular mechanisms underlying psychiatric disorders and commensurate nanotherapeutics for neuropsychiatry: The mind knockout.

Bio-neuronal led psychiatric abnormalities transpired by the loss of neuronal structure and function (neurodegeneration), pro-inflammatory cytokines, microglial dysfunction, altered neurotransmission, toxicants, serotonin deficiency, kynurenine pathway, and excessively produced neurotoxic substances. These uncontrolled happenings in the etiology of psychiatric disorders initiate further changes in neurotransmitter metabolism, pathologic microglial, cell activation, and impaired neuroplasticity. Inflammatory cytokines, the outcome of dysfunctional mitochondria, dysregulation of the immune system, and under stress functions of the brain are leading biochemical factors for depression and anxiety. Nanoscale drug delivery platforms, inexpensive diagnostics using nanomaterials, nano-scale imaging technologies, and ligand-conjugated nanocrystals used for elucidating the molecular mechanisms and foremost cellular communications liable for such disorders are highly capable features to study for efficient diagnosis and therapy of the mental illness. These theranostic tools made up of multifunctional nanomaterials have the potential for effective and accurate diagnosis, imaging of psychiatric disorders, and are at the forefront of leading technologies in nanotheranostics openings field as they can collectively and efficiently target the stimulated territories of the cerebellum (cells and tissues) through molecular-scale interactions with higher bioavailability, and bio-accessibility. Specifically, the nanoplatforms based neurological changes are playing a significant role in the diagnosis of psychiatric disorders and portraying the routes of functional restoration of mental disorders by newer imaging tools at nano-level in all directions. Because of these nanotherapeutic platforms, the molecules of nanomedicine can penetrate the Blood-Brain Barrier with an increased half-life of drug molecules. The discoveries in nanotheranostics and nanotherapeutics inbuilt unique multi-functionalities are providing the best multiplicities of novel nanotherapeutic potentialities with no toxicity concerns at the level of nano range.

Smart Releasing CuS/ZnS Nanocomposite Dual Drug Carrier and Photothermal Agent for Use as a Theranostic Tool for Cancer Therapy

Smart Releasing CuS/ZnS Nanocomposite Dual Drug Carrier and Photothermal Agent for Use as a Theranostic Tool for Cancer Therapy

Enhanced Gold Nanoparticle-Tumor Cell Recognition by Albumin Multilayer Coating

Nanomedicines are studied for application in the diagnosis and treatment of cancer, especially as nanoparticles (NPs). Inorganic NPs open new alternatives based on the properties of high atomic weight elements at the nanoscale as potential theranostic tools. However, NPs are rapidly coated with serum proteins in a biological environment called the Corona effect. This effect affects NPs transport through biological medium and cellular uptake and response, having significant consequences in therapeutic efficiency. Also, NP decoration with specific ligands to recognize cell surface receptors of tumor cells, is not enough to overcome this problem. This is currently the most critical issue to overcome for in vivo application of NPs. The extraordinary 3D arrangement of atoms in the protein structure is far from the current human ability to prepare nanomaterials. Therefore, we propose to use albumin, the natural carrier of the blood, as a building block to prepare ‘stealth’ NPs with the ability to avoid non-specific interactions with the biological media. Biohybrid NPs (bioHNPs) are prepared by coating AuNPs with a multilayer of albumin by dynamic aggregation and radiation-induced crosslinking method. Experimental data of NPs/biological media interaction, measured by changes in the hydrodynamic radii, shows a substantial reduction of the Corona effect of bioHNPs under in vitro biological conditions. In addition, Bombesin-decorated bioHNPs offer an enhanced NP uptake to PC-3 cell cultures, containing specific membrane receptors for Bombesin, using near-physiological conditions. This novel preparation method of crosslinked multilayer coating and decoration can be extended to other inorganic nanoparticles to improve biocompatibility.