Inorganic-Organic Hybrid Nanoparticles—High-Load Drug Carriers with Theranostic Features

Inorganic-organic hybrid nanoparticles (IOH-NPs) basically have a composition [M]²⁺[<i>R_Drug</i>OPO₃]^2- and contain a drug anion [<i>R_Drug</i>OPO₃]²^- and an inorganic cation (e.g., [ZrO]²⁺, [La(OH)]²⁺, [GdO]⁺, [Bi(OH)]²⁺).¹ The inorganic cation guarantees the insolubility of the IOH-NPs in water and allows the nucleation of nanoparticles with high colloidal stability in aqueous suspensions. Due to the saline composition with equimolar amounts of drug anion and inorganic cation, IOH-NPs exhibit unprecedented high drug loads of 70-90% of the total nanoparticle mass.^1,2<br/>Specific examples are [ZrO]²⁺[BMP]²^-, [ZrO]²⁺[CLP]²^- or [ZrO]²⁺[FdUMP]²^- with the anti-inflammatory agent betamethason phosphate (BMP) (81 wt-% per nanoparticle), the last-line antibiotic clindamycin phosphate (CLP) (82 wt-% per nanoparticle), or the cytostatic agent 5’-fluoro-2’-deoxyuridine 5’-monophosphate (FdUMP) (75 wt-% per nanoparticle). <i>In vitro</i> and <i>in vivo</i> studies show high uptake as well as excellent biocompatibility and activity. The IOH-NP concept has been transferred to &gt;50 different nanoparticles and drugs, and offers widespread advantages:^1,2<br/>- New patented class of materials<br/>- Easy synthesis in water<br/>- Extremely high drug load (70-90 % of total nanoparticle mass)<br/>- Platform concept with flexible composition<br/>- Realization of drug cocktails, optionally with chemotherapeutic, antibiotic, antiviral or anti-inflammative agents in one nanoparticle<br/>- Higher efficacy and/or significantly lower side effects due to targeted transport of the chemotherapeutic cocktail into the tumor<br/>- Transport of active agent (instead of prodrugs)<br/>- Simultaneous release (in time and in place) of drug cocktail for effective reduction of resistances (in general) and metastases (cancer)<br/>Localization and tracking of drug release by imaging methods (OI, PAI, MRI, PET)<br/>With this contribution, we present the current status and perspectives of the IOH-NPs with drug cocktails.<br/><br/><b>References </b><br/>[1] J. G. Heck, J. Napp, S. Simonato, J. Möllmer, M. Lange, H. R. Reichardt, R. Staudt, F. Alves, C. Feldmann, <i>J. Am. Chem. Soc. </i><b>2015</b>, <i>137</i>, 7329-7336.<br/>[2] (a) C. Ritschel, J. Napp, F. Alves, C. Feldmann, <b>2022</b>, <i>submitted</i>. (b) K. Sabljo, J. Napp, F. Alves, C. Feldmann, <i>Chem. Commun.</i> <b>2022</b>, <i>in revision</i>. (c) B. L. Neumeier, J. G. Heck, C. Feldmann, <i>J. Mater. </i><i>Chem. C</i> <b>2019</b>, <i>7</i>, 3543-3552. (d) J. Napp, M. A. Markus, J. G. Heck, C. Dullin, W. Möbius, D. Gorpas, C. Feldmann, F. Alves, <i>Theranost. </i><b>2018</b>, <i>8, </i>6367-6368. (e) M. Poß, E. Zittel, C. Seidl, A. Meschkov, L. Muñoz, U. Schepers, C. Feldmann, <i>Adv. </i><i>Funct. Mater. </i><b>2018</b>, <i>28</i>, 1801074(1-8). (f) M. Poß, R. J. Tower, J. Napp, L. C. Appold, T. Lammers, F. Alves, C.-C. Glüer, S. Boretius, C. Feldmann, <i>Chem. </i><i>Mater. </i><b>2017</b>,<i> 29</i>, 3547-3554.