Theranostic nanoplatforms with integrated diagnostic and therapeutic functions, aiming at imaging-guided therapy to improve treatment planning, as well as combination therapy to enhance treatment efficacy, have received tremendous attention in recent years. Among numerous types of functional nanomaterials explored in this field, protein-based nanocarriers with inherent biocompatibility have also been selected as building blocks to construct multifunctional theranostic platforms. In particular, albumin, which has been extensively used as drug-delivery carriers for decades, has shown great new promise in the construction of novel imaging and therapeutic nanoagents, as demonstrated by a number of recent studies. IHere, the motivations of using albumins to build up nanoscale theranostics are discussed, and the latest progress/future perspectives in this direction are summarized.
Recent advances in the development of magnetic nanoparticles (MNPs) have shown promise in the development of new personalized therapeutic approaches for clinical management of cancer patients. The unique physicochemical properties of MNPs endow them with novel multifunctional capabilities for imaging, drug delivery and therapy, which are referred to as theranostics. To facilitate the translation of those theranostic MNPs into clinical applications, extensive efforts have been made on designing and improving biocompatibility, stability, safety, drug-loading ability, targeted delivery, imaging signal and thermal- or photodynamic response. In this review, we provide an overview of the physicochemical properties, toxicity and theranostic applications of MNPs with a focus on magnetic iron oxide nanoparticles.
- Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging
- Published over 2 years ago
The fields of biomedical nanotechnology and theranostics have enjoyed exponential growth in recent years. The “Molecular Imaging in Nanotechnology and Theranostics” (MINT) Interest Group of the World Molecular Imaging Society (WMIS) was created in order to provide a more organized and focused forum on these topics within the WMIS and at the World Molecular Imaging Conference (WMIC). The interest group was founded in 2015 and was officially inaugurated during the 2016 WMIC. The overarching goal of MINT is to bring together the many scientists who work on molecular imaging approaches using nanotechnology and those that work on theranostic agents. MINT therefore represents scientists, labs, and institutes that are very diverse in their scientific backgrounds and areas of expertise, reflecting the wide array of materials and approaches that drive these fields. In this short review, we attempt to provide a condensed overview over some of the key areas covered by MINT. Given the breadth of the fields and the given space constraints, we have limited the coverage to the realm of nanoconstructs, although theranostics is certainly not limited to this domain. We will also focus only on the most recent developments of the last 3-5 years, in order to provide the reader with an intuition of what is “in the pipeline” and has potential for clinical translation in the near future.
The development of imageable photothermal theranostics has attracted considerable attention for imaging guided photothermal therapy (PTT) with high tumor ablation accuracy. In this study, we strategically constructed a near-infrared (NIR) cyanine dye by introducing a rigid cyclohexenyl ring to the heptamethine chain to obtain a heptamethine dye CySCOOH with high fluorescence intensity and good stability. By covalent conjugation of CySCOOH onto human serum albumin (HSA), the as-prepared HSA@CySCOOH nanoplatform is highly efficient for NIR fluorescence/photoacoustic/thermal multimodality imaging and photothermal tumor ablation. The theranostic capability of HSA@CySCOOH was systematically evaluated both in vitro and in vivo. Most intriguingly, complete tumor elimination was achieved by intravenous injection of HSA@CySCOOH (CySCOOH, 1 mg kg(-1); 808 nm, 1.0 W cm(-2) for 5 min) into 4T1 tumor-bearing mice, with no weight loss, noticeable toxicity, or tumor recurrence being observed. This as-prepared protein-based nanotheranostics exhibits high water dispersibility, no off target cytotoxicity, and good biodegradability and biocompatibility, thus facilitating its clinical translation to cancer photothermal theranostics.
Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action.
A variety of nanoplatforms have been developed and applied for cancer therapy, imaging, or the combination thereof. These nanoplatforms, combined with therapeutic and imaging functionalities, display great potential to enhance medical care. In particular, lipid-based nanoparticles (LNPs) are among the most-studied platforms that have resulted in many encouraging advances in theranostics. LNPs are biodegradable and biocompatible, and their formulation can be tailored for various applications. Here, we provide an overview of recent developments of four representative LNP platforms for theranostics: stealth liposomes, triggered-release liposomes, porphysomes, and lipid-coated calcium phosphate NPs (LCPs). We discuss their potential, limitations, and potential applications for cancer care and highlight perspectives and future directions for the nanotheranostics field.
“Smart” bioresponsive materials, which are sensitive to biological signals or pathological abnormalities, are appealing therapeutic platforms for the development of next-generation cancer theranostics. In this work, a novel “stepwise extraction” strategy has been proposed and demonstrated in constructing injectable bioresponsive composite implant, which features unique theranostic responsivenesses to exogenous and external triggers. The as-designed implant exhibits theranostic functions and biodegradability for cancer treatment based on the change of intratumoral microenvironment and the needs of therapeutic process. This “stepwise extraction” process, that is, “solvent extraction”, “manganese extraction” and “phosphorus extraction”, significantly promoted the biodegradation and disintegration of the bioresponsive implant step by step, accompanied by the corresponding component releases from the PLGA framework and furthermore, accomplished different specific theranostic functions needed at different treatment stages. This is the first demonstration of bioresponsive organic-inorganic hybrid implant with marked theranostic functions and excellent biodegradability by a “stepwise extraction” approach, paving the way to the solutions of unsatisfactory therapeutic efficacy and strong side effects in current cancer therapeutic modalities.
As an emerging field that is receiving an increasing amount of interest, theranostics is becoming increasingly important in the field of nanomedicine. Among the various smart platforms that have been proposed for use in theranostics, polymer vesicles (or polymersomes) are among the most promising candidates for integration of designated functionalities and modalities. Here, a brief summary of typical theranostic platforms is presented with a focus on modular polymer vesicles. To highlight modularity, the different methodologies for designing therapeutic and diagnostic modules are classified and current examples of theranostic vesicles that excel in both performance and design principle are provided. Finally, future prospects for theranostic polymer vesicles that can be readily prepared with functional modules are proposed. Overall, theranostic polymer vesicles with modular modalities and functions are more promising in nanomedicine than simply being “over-engineered”.
Significant preclinical and clinical research has explored the use of magnetic iron oxide nanoparticles (MNPs) for medical theranostics. Herein, we provide an overview of the optimal ‘design-to-perform’ MNPs used in cancer therapeutics, specifically focusing on magnetic hyperthermia, magnetic drug targeting, and targeting delivery. An account of the progress made in the clinic using MNPs is then analyzed. We place special emphasis on past and present magnetic nanoformulations used in clinical settings or yet to be clinically approved. Regrettably, as of now, no MNP drug delivery system is employed in the clinic. Thus, identifying current limitations, misconceptions and challenges will definitely impact the clinical success of MNP delivery theranostic systems and their promising future potential in medicine.
Intelligent polymeric nanogels, with the rationally designed stimuli-responsive drug delivery and controlled drug release, have attracted considerable attention as an ideal nanoplatform for activatable therapy. On the other hand, functional inorganic nanomaterials are widely used as medical imaging agents due to their unique magnetic or optical properties. The construction of stimuli-responsive polymeric nanogels incorporating with functional inorganic nanomaterials inherits the excellent properties of both polymers and inorganic nanomaterials, consequently, the resulted organic-inorganic hybrid nanogels naturally exhibit stimuli-responsive multi-functionalities for both imaging and therapy. In this review, we summarize the recent advance of stimuli-responsive organic-inorganic hybrid nanogels. Firstly we discuss the physical and chemical methods thus far developed for the integration of polymeric nanogels and inorganic nanomaterials, and then we show the typical examples of activatable theranostic applications using organic-inorganic hybrid nanogels. In the end, the existing challenges and future directions are briefly discussed.